Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 1) and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.7, of Regulation (EC) No 1907/2006).
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Toxicity to reproduction – Fertility

Screening

A reproductive/developmental toxicity screening test according to OECD 421 was conducted with the test substance in male and female rats (Holalagoudar, 2012). The test substance formulated in sterile water was administered once daily via oral gavage to 10 Wistar rats per sex and group at dose levels of 100, 300, 1000 mg/kg bw/day, respectively. A similar constituted group of animals received the vehicle only and served as control. Treatment was performed during 14 days pre-mating and 14 days mating period in both male and in female rats, as well as during gestation period and up to post-natal day (PND) 3 in female rats. During the study period, no treatment-related mortalities and no predominant clinical signs of toxicity were observed in parental animals of the treatment groups compared to the controls. Furthermore, no effect on food consumption and body weight was noted in treated groups when compared with controls. Gross pathology of parental animals revealed reddish discoloration of various organs (e.g. kidney, skin, and testis) in a dose-related manner among all treated groups, which was considered to be due to the specific red colour of the test substance. Other macroscopic organ findings were very few and not regarded to be treatment-related, including a yellow spot in the epididymis of 2/10 males of the control group and 1/10 male receiving 100 mg/kg bw/day, which represented spontaneous spermatic granuloma(s). In males, a statistically significant increase in absolute and relative organ weight of prostate (including seminal vesicle with coagulating gland) was observed at 1000 mg/kg bw/day. However, no corresponding microscopic findings in prostate (including seminal vesicle with coagulating gland) were observed at any dose level, thus the changes in prostate weight were considered to be non- adverse. There were no treatment-related effects observed in testes and epididymides weights of treated groups compared to the controls. In females, no statistically significant differences in the absolute and relative organ weight of reproduction organs (ovaries, uterus with oviduct and cervix) were noted in treatment groups compared with controls. In accordance with the observed substance-related reddish discoloration of some organs at necropsy, brown and red-brown pigments were observed in reproduction organs and kidney as well as in a number of lymph nodes at microscopic examination. However, in view of the low degree of severity observed and in the absence of any changes indicating functional impairment of the organs, the pigmentation was not considered to be of toxicological relevance. There was no treatment-related effect observed on the duration of gestation and pre-coital interval in the treated groups when compared with controls. The copulation index, fertility index and viability index in treated groups remained unaffected compared to the control. All pregnancies resulted in normal births and therefore delivery index was not affected in any treatment group. The mean number of corpora lutea, implantation sites, and live pups born on PND 0 as well as the percent pre-implantation loss and post-implantation loss in treated groups were comparable to those of controls. There was no treatment-related effect observed on total number of pups born, sex ratio, live pups, still birth on PND 0 and total number of live pups and sex ratio on PND 4. Furthermore, no treatment-related gross external findings were observed in pups from the treated groups on PND 0 and 4. Based on the results of this study, the NOAEL for developmental and maternal toxicity in rats treated with the test substance was considered to be ≥ 1000 mg/kg bw/day.


Short description of key information:
NOAEL (systemic and reproductive toxicity, rat, m/f) = 1000 mg/kg bw/day (OECD 421)

Justification for selection of Effect on fertility via oral route:
There is only one study available.

Justification for selection of Effect on fertility via inhalation route:
Study not required according to Annex VIII of Regulation (EC) No. 1907/2006.

Justification for selection of Effect on fertility via dermal route:
Study not required according to Annex VIII of Regulation (EC) No. 1907/2006.

Effects on developmental toxicity

Description of key information
NOAEL (developmental toxicity, rat, m/f) = 1000 mg/kg bw/day (OECD 421)
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 1) and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.7, of Regulation (EC) No 1907/2006).
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information
Justification for selection of Effect on developmental toxicity: via oral route:
There is only one study available.

Justification for selection of Effect on developmental toxicity: via inhalation route:
Study not required according to Annex VIII of Regulation (EC) No. 1907/2006.

Justification for selection of Effect on developmental toxicity: via dermal route:
Study not required according to Annex VIII of Regulation (EC) No. 1907/2006.

Justification for classification or non-classification

Based on the available data on reproductive toxicity, the test substance does not meet the criteria for classification according to Regulation (EC) No 1272/2008 or Directive 67/548/EEC.