Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

In this 2-generation study equivalent to OECD 416, treatment of groups of male and female rats of both the P0 and P1b generations with the test substance at dosages of 1000, 5000 or 10000 ppm, incorporated in the diet, did not cause any significant effects upon mortality, clinical condition, body weight, food consumption or pathological status. There were neither significant adverse effects upon reproductive performance nor development of the pups in the F1a, F1b, F2a or F2b generations (American Cyanamid Company, IZ-430 -001, 1987)

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
835.65 mg/kg bw/day
Study duration:
chronic
Species:
rat
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

In a two generation study equivalent to OECD guideline 416, groups of 25 male and 25 female CD (Sprague-Dawley) rats, forming the P0 generation, were treated with the test substance, by dietary incorporation, at dosages of 0, 1000, 5000 and 10000 ppm (American Cyanamid Company, IZ-430 -001, 1987). The animals were treated for 64 days prior to placement for mating, throughout the two mating periods and until necropsy, approximately 3 weeks after the end of the second mating period. The females were also treated throughout gestation and lactation. On day 21 post partum, the F1b generation litters were weaned and 25 males and 25 females were selected for each group to form the P1b adult generation. These animals were treated with the test substance in a manner identical to that of their parents for at least 78 days prior to mating and provided the F2 generations. The treatment of the P1b generation adult females was continued throughout the mating, gestation and lactation periods. The P1b generation adult males were treated until necropsy, approximately 4 weeks after the end of the second mating period. The F2 generation pups were killed following weaning.

There were no deaths, clinical signs or pathological findings which were considered related to treatment with the test substance.

Treatment with the test substance did not affect either the body weights or the food intake of the males and females. The range of weekly achieved intakes of test substance in the 1000, 5000 and 10000 ppm groups, respectively, was as follows: P0 generation males 74.3, 380.5 and 738 mg/kg bw/day; P0 generation females 94.3, 471.2 and 933.3 mg/kg bw/day; P1b generation males 83.8, 418.4 and 849.9 mg/kg bw/day; P1b generation females 102, 515.3 and 1026.4 mg/kg bw/day.

The conception rate for the first mating period of the P0 generation at the 10000 ppm level was significantly (P < 0.05) decreased. Taking values for the second mating period into consideration in combination with values of the first mating period indicates this not to be of toxicological significance. There were no significant differences in the fertility indices, day of mating or other parameters of parental performance. There were marked inter-group variations in the incidence of dead pups at birth which on occasion attained statistical significance; however, there was no consistent trend indicative of a treatment relationship. Other parameters of maternal performance including gestation index, length of gestation, number-of live pups at birth and sex ratio were similar to control values.

The viability, survival and lactation indices were unaffected, as was the clinical condition of the pups in the treated groups. On all but one occasion, the pup body weights in the treated groups were not significantly different from control values. There were no pathological findings related to treatment.

Treatment of groups of male and female rats of both the P0 and P1b generations did not cause any significant effects upon mortality, clinical condition, body weight, food consumption or pathological status. Neither were there significant adverse effects upon reproductive performance nor development of the pups in the F1a, F1b, F2a or F2b generations.

In conclusion, there were no treatment related signs of systemic toxicity and no adverse effects on reproductive performance or pup development at dietary levels up to 10000 ppm, the highest dose tested.

Justification for classification or non-classification

The available study is reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance does not need to be classified and labelled for reproductive toxicity under Regulation (EC) No 1272/2008, as amended for the ninth time in Regulation EC No 2016/1179.