Methacrylic acid, monoester with propane-1,2-diol

NOAEL = 19.2 mg/kg [males] and 23.8 mg/kg [females]) Liver: peroxisome proliferation and ↑ weight (males) from 500 ppm; ↑ weight, adenomas and carcinomas (both sexes) from 1,500 ppm; kidney: ↓ weight (especially males) and chronic progressive nephropathy (both sexes) from 1,500 ppm; testes: ↓ weight, ↑ incidence and severity of bilateral hypospermia from 1,500 ppm; epididymis: ↑ immature or abnormal sperm forms and hypospermia from 1,500 ppm; ↓ survival (males); changes in liver, kidneys, and testes were at least partially reversible following recovery period
overall effects: the mean body weight gains of male groups that received 12500 or 50000 ppm were significantly less than those of the controls. No chemical-related clinical findings were observed. No biologically significant changes in final mean body weights, absolute or relative organ weights, or hematology or clinical chemistry parameters were noted in any dose group.
The oral administration of Ametryn Technical at the dose of 100 ppm had no effects on general health, growth, food consumption, pre-terminal deaths and life expectancy, differential leukocyte count values, and changes in organ weights. No gross or histopathological changes seen were attributable to the test substance.
No effect on general health, body weights, net weight gains, food consumption, organ weights and organ weight ratios in both the sexes except an incidental decrease in mean body weights on week 3 and decreased body weight gains in males at the 675 ppm dose level.  NOEL of Ametryn Technical in Swiss albino mice was 225 ppm in the food which is equivalent to 44.8, 51 .8 and 48.3 mg/kg Bwt/day for males, females and combined sex respectively under the testing conditions described in the material and method section and the doses employed.
No effect on general health status, growth, hematological and clinical chemistry parameters, organ weights, and histopathological changes at the low-dose (150 ppm) group.  Adverse effects reported in mid-dose (600 ppm) and high-dose (2400 ppm) groups.
Liver: ↑ weight (males) and peroxisome proliferation at 500 ppm; kidney: ↑ weight from 2,500 ppm; ↑ mineralization of the renal papilla (males), tubule cell pigment (both sexes), and chronic progressive nephropathy (males) at 12,500 ppm; pituitary: ↑ castration cells (30/60 males) ar 12,500 ppm; testes: ↓ weight, ↑ incidence and severity of bilateral aspermatogenesis; ↓ incidence of interstitial cell neoplasms; epididymis: ↑ immature or abnormal sperm forms and hypospermia from 12,500 ppm; changes in the kidneys, testes, and pituitary were not reversible upon cessation of exposure
Mortality was significantly increased.  A statistically significant decrease in body weight, increase in urinary pH and presence of occult blood in the urine was also noted.  There was also a significant increase in non-neoplastic and neoplastic lesions of the bladder and urinary system.
The NOAEL of 150 mg/kg/day is the same as that reported after 16-week exposure and appears to be a threshold dose below which no renal toxicity occurs, regardless of exposure duration.
Sodium chlorite treatment elicited toxicity at 80 and 25 mg/kg/day. At the highest dose level this was characterised by changes in clinical condition, mortality, haematological changes, histopathological abnormalities in the spleen and evidence of irritation of the gastric mucosa. Minor clinical signs and occasional histopathological abnormalities in the stomach mucosa were observed at 25 mg/kg/day.
No treatment-related changes were noted in the 50 and 150 mg/kg bw/day groups in both strains. The Wistar strain was approximately twice as sensitive to the ethylene glycol-mediated crystal nephropathy as the F-344 strain.
No changes in haematology parameters, organ weights in males or histopathological findings were observed at this dose level. The only changes observed at this dose level in the serum chemistry parameters were increases of PL and T-Chol in females; increased relative liver weight was observed in the females. 30 ppm is approximately equivalent to 1.5 mg/kg bw/day.
The only changes observed at this dose level in the serum chemistry parameters were significant increases of PL and T-Chol in both sexes. Increases in relative liver and kidney weights were observed in the females. No histopathological effects were noted. 100 ppm is approximately equivalent to 5 mg/kg bw/day.
In view of the results it is inferred that the oral administration of Ametryn Technical for a period of 24 months at the dose of 75 ppm had no adverse effects on general health, growth, survival and food consumption. There were no treatment related changes in haematology, clinical chemistry and urinalysis. No gross or histopathological changes were attributable to the test substance. Hence this dose, which is equivalent to 3.8, 5.0 and 4.4 mg/kg Bwt/day for males, females and combined sex, respectively was considered as No Observed Effect Level (NOEL) for chronic effects of Ametryn Technical in Wistar rats.
No effect on general health status, body weights and growth and organ weights (excepting for the reduced weights of thymus in males and heart in females).  NOEL is 750 ppm in feed which is equivalent to 86.9, 101.7 and 94.3 mg/kg Bwt/day of the test compound for males, females and combined sex, respectively under the test condition and doses employed.
The NOAEL indicated above was determined based on the findings in the thyroid seen in all males at 10 mg/kg bw/day and higher. In females, thyroid changes were obvious in the mid and high dose group with a dose-dependent increase of incidences. At 10 mg/kg bw/day and above, additionally histopathological findings were found in the liver of males (bile duct hyperplasia) and in splenic pigmentation in females, which was seen as well in males, but only at the highest dose of cyanamide.
see above the effects observed in this dose group were not considered toxicologically relevant in the absence of any other relevant indications of impaired liver function in females or in the absence of histopathological changes in the kidneys of males.  High absolute and relative liver and  thyroid weights in the females of the 200 mg/kg dose group and a slight diffuse hyperplasia of the follicular epithelial cells in the thyroid in 2 females at 200 mg/kg bw  were considered treatment related and of toxicological significance.
High absolute and relative liver and  thyroid weights in the females of the 200 mg/kg dose group and a slight diffuse hyperplasia of the follicular epithelial cells in the thyroid in 2 females at 200 mg/kg bw  were considered treatment related and of toxicological significance. However, the effects were slight and were not observed after the 14 day recovery period, suggesting complete reversibility.
The study confirmed the kidney as target for ethylene glycol toxicity and gave no indications of tetraethylene glycol-induced toxic effects.
Increase in heart and testes relative weight and a reduction in liver absolute weight.
Histopathology:  6 males and 3 females in the 2.5%  test article group showed slight degeneration of liver cells.    The 1.25 % dose level, based on average food consumption, and mean weights over the study, was approximately 700 to 800 mg/kg body weight.  The 2.5% dose level was approximately 1400 (males) to 1625 (females) mg/kg per day.
Histopathology:  6 of 3 females in the 2.5% test article group showed slight degeneration of the liver cells compared to control.    The 2.5% dose level, based on average food consumption and mean weights over the study corresponded to approximately 1400 (males) to 1625 (females) mg/kg/day.
On the basis of usual observations (i.e. body weight and food consumption), haematological and blood chemical determinations  and autopsy, liver and kidney weights and the histological examination observations on: liver, kidneys, stomach, small and large intestines, spleen, pancreas, heart, lungs, bone marrow, muscle, brain, spinal cord, bladder, adrenals, thyroid, pituitary, gonads, salivary glands, and lymph nodes.
Reduced  final body weight of 10%  together with reduction body weight gain of 12% observed in male rats administered 12,500 ppm eugenol (equivalent to 1250 mg/kg bw/d) compared to control males were considered as slight treatment-related effect since no chemically-related gross or histopathologic effects were observed among the rats. Expert judgment.
equivalent to 500 ppm; several effects (reduced food consumption and bw gain, clinical signs, hematological and clinicochemical alterations, necropsy findings) were mainly reversible; degeneration in the hepatic epithelium was not completely reversible
There was a significant decrease in the number of total implantation sites per litter, however the lack of associated effects on other reproductive parameters do not allow  for a direct conclusion that this observation has a direct effect on reproduction.
Treatment-related multinucleated hepatocytes of varying numbers were detected in the livers from the mid-dose (T2 = 37.5 mg/kg/day and T3 = 75 mg/kg/day) and high­dose (T4 = 150 mg/kg/day) rats.The "no-toxic-effect" level was considered to be 15 mg/kg/day.
Salivation was seen at 300 mg/kg and above for up to 30 minutes post-dosing.  Body weight inhibition and low food consumption was seen in both sexes at 1000 mg/kg. No effect was seen on haematological parameters. High tissue weights for livers and kidneys in the 1000 mg/kg males corresponded to histological abnormaliites.  Hepatocyte hypertrophy and increase in fatty liver was atrributed to treatment.  Renal papillary necrosis, dilation of tubules, lymphocyte infiltration, basophilic tubules and hyaline cast were observed in the kidneys and attributed to treatment. No mortality was observed in this study.
One male and one female at 1000 mg/kg/day were sacrificed for ethical reasons on Day 14 and 24 respectively, showing several clinical signs indicative of ill health. Microscopic examination revealed minimal/slight erosions in the stomach, correlating to the irregular surface recorded at necropsy, slight red pulp atrophy of the spleen and slight/moderate lymphoid atrophy of the thymus, correlating to the reduced size recorded at necropsy. Since these deaths occurred in the highest dose group, and based on clinical signs in the surviving animals at 1000 mg/kg,  a relation to treatment with the test substance cannot be excluded.
salivation, rhinorhea, abnormal respiratory sounds, reduced body weight gain, white blood cell count, platelet count and total serum protein as well as increased segmented neutrophil ratio and increased activity of GPT, GOT and anorganic phosphorus in the serum.
(calculated for the low dose concentration in diet (2000 ppm) based on food consumption) dose-dependent increase in protein resorption droplets was observed in the kidneys, but was, as any other effects, reversible during the following 1-month recovery period