Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

The original study provided by the registrant performed in compliance with the OECD Guideline No. 421 – Reproduction/Developmental Toxicity Screening Test for Anthraquinone with the Good Laboratory Practice (GLP) Regulations was used as a key study for the assessment of human health hazards (Cook J. A., 2010b).

Effects on fertility

In an OECD reproduction toxicity screening test (OECD TG 421) Anthraquinone was studied in rats (strain Sprague Dawley Crl:CD(SD)) orally dosed with 0, 150, 600 and 2400mg/kg bw/day. Duration of the test was 8 weeks; number of animals per dose and sex was 12. Males received Anthraquinone from 14 days prior to pairing and continued untileuthanasia. Femalesreceived Anthraquinone from 14 days prior to pairing through lactation day 4.

The mating, fertility, and fecundity indices (83.3-100%) for both treated males and females were unaffected by treatment with Anthraquinone and were similar to controls (91.7-100.0%). Likewise, the copulatory interval (days to mating) was unaffected by treatment and ranged from 2.4-3.1 days in the treated groups in comparison tothe controls. Treatment did produce a lengthening of the estrous cycle; mean estrous cycle length was significantly increased in the treated females (5.6 days in the 600 mg/kg/day groups) in comparison to controls (4.4 days),but was only significant at 600 mg/kg/day.

Considerable mortality was seen in females at the 600 and 2400 mg/kg/day levels. Several females in the 600 and 2400 mg/kg/day groups died during the gestation and lactation period. At 150 mg/kg/day, no effect of treatment was evident from parturition data. No test article-related organ weight changes were noted in rats of either sex. Test article-related macroscopic changes were noted in female rats, but not in males. Black or red foci were observed in the glandular stomach of females at 600 and 2400 mg/kg/day that died and an erosion/ulcer was noted in the pyloric stomach of one female that died at 2400 mg/kg/day. Also at 2400 mg/kg/day, minimal focal necrosis and moderate periportal vacuolization of hepatocytes were observed in one female, edema was seen in two of seven animals that died, and erosion/ulcer in the glandular stomach was seen in three of these animals. Test article-related microscopic changes were noted in the liver and glandular stomach of female rats at 2400 mg/kg/day, but not in males.

Both male and female rats at all treatment levels were observed with discoloured urine (brown, orange, or red). A treatment-related effect on food consumption was evident in all treated males and females in comparison to controls, although these reductions were not dose-dependent. Decreased body weights were observed in both males and females at all treatment levels. In females, gestation body weight gain was significantly lower than control over most intervals (GD 0-7, 7-14, 14-20, and 0- 20) in the 600 and 2400 mg/kg/day groups. Body weight gain in the 150 mg/kg/day group during lactation was comparable to controls.In addition, decreased activity was observed in four and five females in the 600 and 2400 mg/kg/day groups, respectively, and one male in the 150 mg/kg/day group.

Since both, male and female rats at all treatment levels were observed with discoloured urine and decreased body weights and food consumption; a No-Observed-Effect-Level (NOEL) was not achieved(Cook J. A., 2010b).

Developmental toxicity/teratogenicity

In an OECD reproduction toxicity screening test (OECD TG 421) Anthraquinone was studied in rats (strainSprague Dawley Crl:CD(SD))orally dosed with0, 150, 600 and 2400mg/kg bw/day. Duration of test was 8 weeks. Number of animals per dose and sex was 12. Males received Anthraquinone from 14 days prior to pairing and continued untileuthanasia. Femalesreceived Anthraquinone from 14 days prior to pairing through lactation day 4.

At 150 mg/kg/day, no effect of treatment was evident from litter size, or pup survival to LD 4.The number of pups born, liveborn, and stillborn in the 150 mg/kg/day group was similar to controls and unaffected by treatment. Pup survival (to LD 4) in the 150 mg/kg/day group was 89% and was comparable to the controls at 97%, but itwas poor in the 600 and 2400 mg/kg/day groups.Very few pups survived to LDthe 2400 mg/kg/day group, but no clinical observations were noted for these pups.Pup body weights were decreased at all treatment levels; mean pup body weights in the 150 mg/kg/day group were similar to control at birth (LD 0), but 8-10% lower by LD 4.Pup sex ratio (% males per litter) in the treated groups was considered comparable to controls and unaffected by treatment. No macroscopic observations were evident in any pups at necropsy(Cook J. A., 2010b).


Short description of key information:
The test substance, Anthraquinone was tested for reproduction toxicity using the OECD Test Guideline No. 421 Reproduction/Developmental Toxicity Screening Test.
Based on the study provided by the registrant , NOAEL was not defined due to the fact, that there were health effects regarding general toxicity in both, male and female rats present at all treatment levels.
Mating, fertility, and fecundity indices and copulatory interval in all treatment groups were comparable to controls.
Considering developmental toxicity, pup body weights were decreased at all treatment levels and pup survival was poor in the 600 and 2400 mg/kg/day groups, but no further clinical observations were noted for the pups (Cook J. A., 2010b).

Effects on developmental toxicity

Description of key information
The study is waived because there is enough data available; substance is considered not toxic to reproduction.
There is information on developmental toxicity available from reproduction toxicity screening test (OECD TG 421).
Additional information

In an OECD reproduction toxicity screening test (OECD TG 421) Anthraquinone was studied in rats (strain Sprague Dawley Crl:CD(SD))orally dosed with 0, 150, 600 and 2400mg/kg bw/day. Duration of test was 8 weeks. Number of animals per dose and sex was 12. Males received Anthraquinone from 14 days prior to pairing and continued until euthanasia. Females received Anthraquinone from 14 days prior to pairing through lactation day 4.

At 150 mg/kg/day, no effect of treatment was evident from litter size, or pup survival to LD 4.The number of pups born, liveborn, and stillborn in the 150 mg/kg/day group was similar to controls and unaffected by treatment. Pup survival (to LD 4) in the 150 mg/kg/day group was 89% and was comparable to the controls at 97%, but itwas poor in the 600 and 2400 mg/kg/day groups.Very few pups survived to LD the 2400 mg/kg/day group, but no clinical observations were noted for these pups. Pup body weights were decreased at all treatment levels; mean pup body weights in the 150 mg/kg/day group were similar to control at birth (LD 0), but 8-10% lower by LD 4. Pup sex ratio (% males per litter) in the treated groups was considered comparable to controls and unaffected by treatment. No macroscopic observations were evident in any pups at necropsy (Cook J. A., 2010b).

Justification for classification or non-classification

Based on the test results and according to the EC criteria for classification and labelling requirements for dangerous substances and mixtures the test substance Anthraquinone does not have to be classified for toxicity to reproduction.