Registration Dossier

Administrative data

Description of key information

Acute oral: 950 mg/kg bw < LD 50< 1397 mg/kg bw (Similar to OECD TG 401; BASF SE, 1977)
Acute dermal: LD 50 > 200 mg/kg bw (OECD 402; Air Products & Chemicals Inc, 2007)

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable study report wich meets basic scientific principles, however with the following restriction: Minimal details on test animals were given.
Principles of method if other than guideline:
BASF Test:
Several groups of 5 rats were treated by gavage with suspensions of the test substance in 0.5% Carboxylmethyl cellulose (CMC) aqueous preparation. Group-wise documentation of clinical signs was performed over the 14-day study period. Body weight was determined before the start of the study only, as it was needed for determination of dose. The clinical signs and findings were reported in summary form.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: males 202 g, females 170 g (mean)
- Diet: Altromin R 124 (Altromin GmbH, Lage)

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Doses:
647, 950, 1397, 2043, 3002 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Statistics:
Probit analysis was used for the determination of the LD50.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 1 140 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 950 mg/kg bw < LD 50< 1397 mg/kg bw
Mortality:
3002 and 2043 mg/kg bw: all animals died
1397 mg/kg bw: all male animals and 4/5 female animals died
950 mg/kg bw: 1/5 males died, all females survived
647 mg/kg bw: all animals survived
Clinical signs:
Dyspnoea, poor general state, apathy, abdominal or lateral position, spastic gait, atonia, and diarrhoea were noted in the 1397, 2043 and 3002 mg/kg bw dose groups.
Body weight:
Body weight decrease was observed during the study.
Gross pathology:
Necropsy findings of the animals that died comprised erythema of the intestinal mucosa, acute congestive hyperemia and dilatation of the heart, acute cachexia.

Dose

(mg/kg bw)

 

Mortality

Dead/Treated

1 hour

24 hours

48 hours

7 days

14 days

male

female

male

female

male

female

male

female

male

female

647

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

950

0/5

0/5

0/5

0/5

0/5

0/5

1/5

0/5

1/5

0/5

1397

0/5

0/5

1/5

2/5

3/5

2/5

5/5

4/5

5/5

4/5

2043

0/5

0/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

3002

1/5

0/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 140 mg/kg bw
Quality of whole database:
Acceptable, well-documented study report.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
200 mg/kg bw
Quality of whole database:
Acceptable, well documented study report.

Additional information

Oral exposure

The potential of the test substance (purity >97%) to induce acute oral toxicity was evaluated in male and female SD rats in a test protocol conducted similar to the OECD TG 401 with acceptable deviations (BASF SE, 1977). Groups of 5 rats per dose were treated by gavage with suspensions of the test substance in 0.5% Carboxylmethyl cellulose (CMC) aqueous preparation at dose levels of 647, 950, 1397, 2043, and 3002 mg/kg bw. Group-wise documentation of clinical signs was performed over the 14-day study period. Body weight was determined before the start of the study only, as it was needed for determination of dose. The clinical signs and findings were reported in summary form. All animals died in the 2043 and 3002 mg/kg bw dose groups within 24 hours , 5/5 males and 4/5 females in the 1397 mg/kg bw dose group within 7 days, and 1/5 males in the 950 mg/kg bw dose group within 7 days. No animal died in the low dose group. Clinical signs included dyspnoea, poor general state, apathy, abdominal or lateral position, spastic gait, atonia, and diarrhea, generally noted in the 1397, 2043 and 3002 mg/kg bw dose groups. Body weights generally decreased during the course of the study. Erythema of the intestinal mucosa, acute congestive hyperemia, dilatation of the heart, and acute cachexia were generally observed at necropsy in the animals that died.

Therefore, based on the results of the study, an acute oral LD50 > 950 mg/kg bw and < 1397 mg/kg bw was assumed after administration to rats.

Dermal exposure

The potential of the test substance to induce acute dermal toxicity was evaluated in 2 studies (2 batches were tested) in a test protocol conducted according to the OECD TG 402 (Air Products & Chemicals, Inc., 2007) in healthy male and female New Zealand White rabbits (2 males and 3 females in the first study [Project number MB 07-16376.02, TS purity = 83.4%] and in 3 males and 2 females in the second study [Project number MB 07-16377.02, TS purity = 92.2%]). The animals were dosed with a unique dose of 200 mg/kg bw under semiocclusive coverage for 24 hours, and observed for toxicity and pharmacological effects at 1, 2 and 4 hours post-dose and once daily for 14 days. All animals were also observed twice a day for mortality and body weights were recorded pretest, weekly and at termination. At termination, all animals were examined for gross pathology and abnormal tissues were preserved in 10% neutral buffered formalin for possible future histological examination. All Animals survived the 200 mg/kg bw dermal application of the test substance. Only one animal of the first study appeared lethargic on the day of treatment (Day 0). There were no further adverse clinical effects and body weight changes were normal in both studies. Severe dermal effects (necrosis) were observed after 24 hours, on days 11 and 14, and at necropsy. No further adverse effects were observed at necropsy. Therefore, based on the observed results, the dermal LD50 of test substance after acute dermal application to rabbits appeared to be greater than 200 mg/kg bw.

The acute dermal toxicity of the test substance (TS purity >97%) was also evaluated in rabbits in a test protocol conducted similar to the OECD TG 402 with acceptable deviations (BASF SE, 1977). 3 male and 3 female rabbits were treated with 190 mg/kg bw test substance applied to a haven skin site on their back for 24 h under occlusive conditions. The animals were observed for 14 days for mortality and clinical signs of toxicity, and those animals that died during the course of the study were submitted to necropsy. Survived animals were also subjected to gross-pathological examination. One male animal was found dead within 48 hours after treatment and a total of 3 animals (2 males and 1 female) died up to the end of the observation period. Clinical signs of toxicity included apathy, dispnoea, cyanosis, tremor, piloerection, blood-coloured urine with hematoma and poor general state. Local signs of irritation included erythema, edema, necrosis and desquamation observed in all animals. Based on the results of the study an acute dermal LD50 of approx. 190 mg/kg bw after administration of test substance to rabbits.

Taken together all data the acute dermal LD50 is estimated to be greater than 200 mg/kg bw.

Inhalation exposure

No reliable data available. One disregarded study done by BASF in 1977 is available.

The animals were exposed to the saturated vapours generated from a test substance with very low vapour pressure. The nominal concentration and saturated concentration (calculated) was approximately 0 mg/L indicating that the animals were not exposed to the vapours. Analytical verification of the test atmosphere was not performed. Keeping in view these methodological deficiencies, the study was considered to be not reliable for the assessment.


Justification for selection of acute toxicity – oral endpoint
Only one study available.

Justification for selection of acute toxicity – dermal endpoint
Key study

Justification for classification or non-classification

Based on the oral LD50, the test substance has to be classified according to EU Annex VI of directive 67/548/EEC (Xn, R22) and 1272/2008/EEC (Cat 4) for the oral route.

Based on the dermal LD50, the test substance has to be classified according to EU Annex VI of directive 67/548/EEC (T, R24) and 1272/2008/EEC (Cat 3) for the dermal route.