Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

Short et al, 1979, was selected as the key study for this endpoint. The study was conducted in a similar manner to the OECD 421 guideline. The test was conducted on rats at concentrations of 0, 19, 39 and 89 ppm for 7 hours/day, 5 days/week. Males and females exposed to concentrations of 39 ppm or below showed comparable results for reproduction to those of the control (0 ppm) group. The NOAEC was therefore selected as 39 ppm. The 89ppm groups showed atrophy of the testes in male animals and an increase in incidence of mild vacuolated degeneration of epithelium of the uterus with/without necrosis and ovarian cysts.

Williams et al (1991), Amir (1975) and El Jack & Hrudka (1979) are presented as supporting information only.

Williams et al, 1991, was conducted on mature male rabbits and examined the effect of the substance on semen and sperm using a novel methodology. Williams et al, 1991, presents a NOAEL value of 15 mg/kg bw/day based upon the criteria examined.

Amir, 1975, was conducted on young and adult bulls, examined quality of seman and sperm, again using a novel methodology. No NOAEL value was determined as only a single treatment level of 4mg/kg bw/day was used.

El Jack & Hrudka, 1979, also examined sperm parameters, however in male sheep (rams). No NOEL was derived, however the registered substance was considered to be teratogenic under the conditions of the test.

Short description of key information:
The key study (Short et al, 1979) reported a NOAEC value of 39ppm. The key study was awarded a reliability score of 2 and was considered both reliable and robust enought to stand as a key study. Several supporting studies giving similar results are also available.

Effects on developmental toxicity

Description of key information
The key study (Short et al, 1977) did not give a NOAEL, however a LOAEL was set at the lowest concentration tested (20ppm). The study report for Short et al, 1977 was awarded the reliability score of 2 due to minor methodological and reporting deficiencies which impacted the reliability of the study to a limited degree.
Additional information

A single study (Short et al, 1977) was available for this endpoint. Short et al, 1977, was awarded a reliability score of 2 as the study predated GLP, but was however conducted at a reputable testing laboratory for a vigilant client (US EPA). The methodology of the study was similar to the OECD 414 guideline (Prenatal developmental toxicity study), however the exposure period was much longer than that of the guideline. Insufficient reporting of methodology and results reduced the reliability of the study to 2 from 1.

The study was conducted on both rats and mice in parallel, both test animals received the same test concentrations of 0, 20, 38 & 80 ppm, 23 hours a day for 10 days, starting from gestation day 6.

Developmental abnormalities and maternal toxicity related to exposure of the test substance were present in both rats and mice at the 20 ppm exposure level. The LOAEC was therefore set at 20 ppm, the lowest concentration tested.

Justification for classification or non-classification

Based upon the above key studies for toxicity to reproduction and developmental toxicity it is evident that adverse effects on parental/maternal fertility take place at concentrations below the the limit of parental/maternal toxicity, however developmental effects are only observed above the level of maternal toxicity and as such cannot be clearly dissociated from maternal toxic effects.

The registered substance therefore fulfills the criteria for classification and should therefore be classified as follows:

Toxic to reproduction, Category 3: R62 Possible risk of impaired fertility according to 67/548/EEC and Category 2: Suspected of damaging fertility according to EC Regulation 1272/2008.