DS-2920A-E

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

valid data obtained from a screening study, sufficient for assessment of the reproduction toxicity potential of the test item.

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 order to get preliminary information on possible effects of the test item Pigment Orange 79 on reproduction and development, a screening test according to the OECD TG 421 (1995) under GLP conditions was performed (BASF 80R0592/11X454, 2012). For this purpose, 4 groups of 11 male and 11 female Wistar rats were treated by gavage with the test item at following dose levels: 0, 100, 300 and 1000 mg/kg bw/day. In fact, the males were treated over a 14-day pre-pairing period and during the pairing period up to one day prior necropsy; the females were treated throughout the pre-pairing, pairing, gestation and lactation period up to the day 3 post partum. The control animals were dosed with the vehicle alone (purified water).

All animals survived the treatment, and stained/discolored red feces were the only clinical sign observed in the treated groups, which was due to the color of the test item and thus not a treatment-related adverse effect.

No treatment-related effects on food consumption, body weight and body weight gain were observed.

No treatment-related effects on reproductive parameters (e.g., mating performance, fertility, corpora lutea count, duration of gestation) were noticed.

No treatment-related effects on the pups were noticed.

Thus, based on the results of the present study, the NOAEL regarding systemic toxicity and reproductive toxicity in male and female Wistar rats was set at 1000 mg/kg bw/day, which was the highest dose level tested.

Short description of key information:
The test item Pigment Orange 79 was examined in the screening test according to the OECD TG 421 (1995) under GLP conditions (Harlan d51520, 2012). The NOAEL regarding systemic toxicity and reproductive toxicity in male and female Wistar rats was set at 1000 mg/kg bw/day, which was the highest dose level tested.

Justification for selection of Effect on fertility via oral route:
New guideline study conducted under GLP conditions

Effects on developmental toxicity

Description of key information

The test item Pigment Orange 79 was examined in the screening test according to the OECD TG 421 (1995) under GLP conditions (Harlan d51520, 2012). The NOAEL regarding developmental toxicity for Wistar rats offspring was set at 1000 mg/kg bw/day, which was the highest dose level tested.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

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

In the screening OECD TG 421 (1995) test conducted under GLP conditions and reported above (Harlan D51520, 2012), the offspring was examined for detection of any treatment-related changes or effects resulting from the treatment of the parental males and females with the test item Pigment Orange 79 by gavage, at dose levels of 0, 100, 300 and 1000 mg/kg bw/day. In fact, the parental males were treated over a 14-day pre-pairing period and during the pairing period up to one day prior necropsy, whereas the females were treated throughout the pre-pairing, pairing, gestation and lactation period up to the day 3 post partum. The control animals were dosed with the vehicle alone (purified water). Within the OECD 421 screening test, the litters were examined for litter size, live births, still births and any gross anomalies. The sex ratio of the pups was recorded, and the pups were weighed individually on day of parturition and on day 1 and 4 post partum. All pups were examined for any structural changes, either at the scheduled necropsy or during the study (day 1 to 4 post partum) if death occurred. Birth index (number of pups born alive as % of implantation) was determined.

The overall mean numbers of living pups per dam at first litter check were 13.0, 12.2, 12.7 and 13.3, whereas birth indices (number of pups born alive as % of implantations) were 94.1%, 91.8%, 89.4% and 93.0% at the dose levels of 0, 100, 300 and 1000 mg/kg bw/day, respectively. There further was no effect on postnatal loss at any dose level. In fact, at 100 mg/kg bw/day, four pups were found dead in one litter at first check. The remaining pups (5 males and 5 females) in this litter were missing on day 2 post partum. This findings was considered to be incidental. Due to this total litter loss, the mean number of postnatal loss was statistically significantly higher at this dose level. The overall mean number of postnatal loss per dam was 0.2, 1.2, 0.5 and 0.3 at 0, 100, 300 and 1000 mg/kg bw/day, respectively. The examination of the pups revealed no treatment-related abnormalities. No effects on pup body weights were noted at any dose level. In fact, mean body weights of pups on day 1 post partum were 5.9, 6, 5.7 and 5.8 g, at the dose levels of 0, 100, 300 and 1000 mg/kg bw/day respectively. The respective body weight gains of the pups during the first 4 days post parturition were +38.1%, +38.2%, +40.7% and +39.3%. The sex ratio was not affected by the treatment at any dose level, since at first litter check, percentages of male pups were 52%, 43%, 54% and 48%, at 0, 100, 300 and 1000 mg/kg bw/day, respectively. Necropsy revealed no abnormalities in the pups at any dose level tested.

Thus, regarding developmental toxicity, the NOAEL under the test conditions of the OECD TG 421 study can be set at 1000 mg/kg bw/day.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available OECD 421 screening test is reliable and suitable for the purpose of classification under Directive 67/548/EEC. Based on the data, classification for reproduction and developmental toxicity is not warranted under Directive 67/548/EEC, as amended for the 28th time in Directive 2001/59/EC.

 

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available OECD 421 screening test is reliable and suitable for the purpose of classification under Regulation (EC) No. 1272/2008. Based on the data, classification for reproduction and developmental toxicity is not warranted under Regulation (EC) no. 1272/2008.