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Administrative data

Description of key information

Acute oral toxicity:

Key study: Test method OECD 423. GLP study. The oral LD50 for the test substance was determined to be greater than 2000 mg/kg bw.

Key study: Test method equivalent to OECD 401. No GLP study. The oral LD50 for the test substance was determined to be greater than 5200 mg/kg bw.

Acute dermal toxicity:

Key study: Extrapolation based on available guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals.

From the available data on an acute oral toxicity study, it is concluded that the oral LD50 for the substance is greater than 2000 mg/kg bw. As recommended in the corresponding guidelines, where data from the oral route is being used as the starting point, if no data are available on oral bioavailability, it is appropriate to assume that 50% of an orally administered dose is systemically available. Since no data is available on skin absorption, the most precautionary default would be to assume 100% absorption by this route although in reality very few substances will cross the skin to this extent. Therefore, based on these assumptions, the dermal LD50 would be greater than 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 December 2009 - 8 January 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test method according to OECD Guideline 423. GLP study.
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Crj: CD(SD)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Japan Charles River Co., Ltd.
- Age at study initiation: 9 weeks old
- Weight at study initiation: 231-233 g (group 1), 224-238 (group 2)
- Fasting period before study: Starved from p.m.5 of the day before dosing to 6 hours after dosing.
- Housing: Individually caged, Stainless steel 325x195x180 mm
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.9-22.6ºC
- Humidity (%): 41-44.%
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours per day (7:00 to 19:00) of artificial lighting
Route of administration:
oral: gavage
Vehicle:
other: 0.5 w/v % methylcellulose solution
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg

CLASS METHOD
- Rationale for the selection of the starting dose: 2000 mg/kg dose was selected based on previous acute toxicity on the analogue Solven Yellow 3 (5, 50, 300 and 2000 mg/kg ) and Solvent Black 5 test (300 and 1000 mg/kg). In the first study, the LDLO was determined to be 1500 mg/kg. In the second study no toxicity was observed at 1000 mg/Kg.
Doses:
2000 mg/kg bw (two steps)
No. of animals per sex per dose:
3 females / group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: General conditions: daily during acclimation, pre-dose, 15 min, 30 min and every hour until 6 hours after administration, twice daily during the observation period, and once before necropsy. Body weight: Days -1, 0 (prior to administration), 1, 4, 7, 10, 13 and 14 (necropsy day)
- Necropsy of survivors performed: Yes (Day 14). Visual inspection of internal organs and tissues; organ weights. No histopathological inspection was considered necessary.
Sex:
female
Dose descriptor:
discriminating dose
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
other: Abnormal stool color (black) was observed in 1 of 6 animal after 3 hours from treatment, and in day 1 (6/6), day 2 (3/6) and day 3 (1/6). No other clinical sign was observed during the 14 day observation period.
Gross pathology:
No abnormal changes were observed at necropsy.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The discriminating dose was determined to be 2000 mg/kg bw in rats.
Executive summary:

An acute toxicity study was performed according to OECD Guideline 423 (GLP study). Six female rats were exposed to a single oral dose of 2000 mg/kg bw in two steps. After the administration of the test item, the animals were observed for 14 days. General and detailed clinical observations were conducted daily during the entire experiment. Body weights of the animals were periodically determined. After the 14-day observation period, the animals were euthanized and subjected to a necropsy and a detailed gross examination. All the animals survived the experiment. Abnormal stool color (black) was only observed at 3 hours and days 1, 2 and 3 after administration. During the 14-day experiment, body weight and body weight gain were found normal. Regarding the gross examinations, no lesions were found . The substance was classified as category 5 or less of the GHS regarding acute toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The selected key study is GLP compliant and of high quality (Klimisch score = 1).

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
other: extrapolation from results obtained by the oral route
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Extrapolation based on available guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals.
Principles of method if other than guideline:
Extrapolation based on available guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals.
GLP compliance:
no
Test type:
other: Extrapolation based on available guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 600 mg/kg bw

Based on available guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals, an extrapolation based on the acute oral toxicity data is calculated for the dermal route.

From the available data on an acute oral toxicity study, it is concluded that the oral LD50 for the substance is greater than 5200 mg/kg bw. As recommended in the corresponding guidelines, where data from the oral route is being used as the starting point, if no data are available on oral bioavailability, it is appropriate to assume that 50% of an orally administered dose is systemically available. Since no data is available on skin absorption, the most precautionary default would be to assume 100% absorption by this route although in reality very few substances will cross the skin to this extent. Therefore, based on these assumptions, the dermal LD50 would be greater than 2600 mg/kg bw.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the assumptions for the extrapolation from the acute oral toxicity data, the dermal LD50 would be greater than 2600 mg/kg bw.
Executive summary:

From the available data on an acute oral toxicity study, it is concluded that the oral LD50 for the substance is greater than 5200 mg/kg bw. As recommended in the corresponding guidelines, where data from the oral route is being used as the starting point, if no data are available on oral bioavailability, it is appropriate to assume that 50% of an orally administered dose is systemically available. Since no data is available on skin absorption, the most precautionary default would be to assume 100% absorption by this route although in reality very few substances will cross the skin to this extent. Therefore, based on these assumptions, the dermal LD50 would be greater than 2600 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
Klimisch 2.

Additional information

Acute oral toxicity:

Key study: OECD 423. GLP study.

The oral LD50 for the test substance was determined to be greater than 2000 mg/kg bw in rats.

Key study: Equivalent to OECD 401. No GLP study.

The oral LD50 for the test substance was determined to be greater than 5200 mg/kg bw.

Acute dermal toxicity:

Key study: Extrapolation based on available guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals.

From the available data on an acute oral toxicity study, it is concluded that the oral LD50 for the substance is greater than 2000 mg/kg bw. As recommended in the corresponding guidelines, where data from the oral route is being used as the starting point, if no data are available on oral bioavailability, it is appropriate to assume that 50% of an orally administered dose is systemically available. Since no data is available on skin absorption, the most precautionary default would be to assume 100% absorption by this route although in reality very few substances will cross the skin to this extent. Therefore, based on these assumptions, the dermal LD50 would be greater than 2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint

The study with the lowest discriminating dose and highest reliability was selected.

Justification for selection of acute toxicity – dermal endpoint

Extrapolation based on available guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals.

Justification for classification or non-classification

Based on the available data, the substance is not classified for acute toxicity according to CLP Regulation (EC) no. 1272/2008.