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Administrative data

Description of key information

The acute oral LD50 is 797 mg/kg bw

The acute dermal LD50 is >10000 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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Description: White waxy solid
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Central Institute for the Breeding of Laboratory Animals TNO, Zeist, the Netherlands
- Weight at study initiation: Males: 260-284g; Females: 154-184g
- Fasting period before study: In the overnight period before treatment till 4 hours after treatment
- Housing: Groups of 5 per sex in stainless steel cages with wire-screen bottom and front
- Diet: The Institute's cereal-based open formula diet for rats and mice, ad libitum
- Water: Tap water, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2
- Humidity (%): 40-60
- Air changes (per hr): about 10
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
other: isopropyl myristate
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 17.5% (w/v)

DOSE VOLUME APPLIED: 4, 4.8, 5.76, 6.91, 8.29 mL/kg bw for the dose groups 700, 840, 1008, 1209, 1451 mg/kg bw, respectively
Doses:
700, 840, 1008, 1209, 1451 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Rats were observed for signs of toxicity during the first 4 post-treatment hours and thereafter at least once daily. Individual body weights of the rats were recorded on day 0, 7, and 14.
- Necropsy of survivors performed: yes
Statistics:
LD50 was calculated according to the method of Weil, C.W. (Biometrics 8 (1952) 249-263)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
797 mg/kg bw
Based on:
test mat.
95% CL:
>= 703 - <= 905
Mortality:
700 mg/kg bw: Males 1/5; Females 2/5
840 mg/kg bw: Males 2/5; Females 5/5
1008 mg/kg bw: Males 2/5; Females 5/5
1209 mg/kg bw: Males 3/5; Females 5/5
1451 mg/kg bw: Males 4/5; Females 5/5
Deaths occurred between 18 hours and 9 days after dosing.
Clinical signs:
Within a few hours after dosing the rats showed sluggishness and piloerection. Later on, haematuria was observed until 2 days after treatment. After a few days, moreover, encrustations around eyes and nostrils, and signs of emaciation were observed. These latter phenomena persisted in all surviving rats the first post-treatment week. In the second post-treatment week the survivors recovered gradually and looked quite healthy again at the end of the observation period.
Body weight:
The individual body weight of the survivors on day 7, revealed growth retardation or weight loss in all survivors. On day 14 the body weight of most of the rats in the higher dose groups were still lower or only slightly higher than the initial weight.
Gross pathology:
Macroscopic examination at autopsy of the rats that died on the first few post-treatment days revealed blood-stained urine in the bladder of all rats. In the rats that died thereafter and in those that survived the observation period no treatment-related gross alterations were found.
Interpretation of results:
Category 4 based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
797 mg/kg bw
Quality of whole database:
Three studies are available. One of these was performed according to OECD guideline and following GLP. This study was selected as key.

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:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Only 7 days observation period, no body weight determination, limited information on effects observed
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Description: Clear liquid (Super saturated)
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 100 - 160 g
- Fasting period before study: overnight
Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Doses:
464, 1000, 2150, 4640, 10000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations: Observations for mortality and signs of effects were made immediately after dosing at one, four, and 24 hours, and once daily thereafter
- Necropsy of survivors performed: yes
Statistics:
Mortality data was analyzed statistically, utilizing the tables of Horn H.J., Biometrics 12, 311, 1956
Key result
Sex:
female
Dose descriptor:
discriminating dose
Effect level:
10 000 mg/kg bw
Based on:
test mat.
Mortality:
464 mg/kg bw: None
1000 mg/kg bw: One animal died 3 days after treatment
2150 mg/kg bw: None
4640 mg/kg bw: None
10000 mg/kg bw: One animal died 5 days after treatment and another 7 days after treatment.
Clinical signs:
464 mg/kg bw: Within 2 hours of treatment, 3 animals exhibited depression and piloerection, but within 24 hours of treatment all animals appeared normal
1000 mg/kg bw: All animals exhibited depression and piloerection within 2 hours of treatment, 3 of whom displayed a red hooding effect 24 hours after dosing. This effect is attributable to a lack of normal preening behavior.
2150 mg/kg bw: None
4640 mg/kg bw: None
10000 mg/kg bw: None
Gross pathology:
Within the two lowest dosage groups (464 and 1000 mg/kg bw) and particularly in the 1000 mg/kg bw level, yellow coloration was noted in the intestines. One animal in the 464 mg/kg bw dosage group exhibited this coloration, and 4 in the 1000 mg/kg bw level. All other animals in the study exhibited to notable necropsy findings, except those expected in the normal autolysis of animals found dead.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
10 000 mg/kg bw
Quality of whole database:
Two studies are available: one is considered to be klimisch 2 and the other klimisch 4.

Additional information

Acute oral toxicity

In an acute oral toxicity study (1985) performed similar to OECD Guideline 401 and following GLP, the test substance was administered by gavage as a 17.5% dilution in isopropyl myristate (IPM) in single doses of 700, 8110, 1008, 1209 or 1451 mg/kg bw to groups of 5 male and 5 female rats and the animals were observed for 14 days. After treatment the rats showed sluggishness, piloerection, haematuria, encrustations around eyes and nostrils and signs of emaciation. These latter phenomena persisted in all surviving rats the first post-treatment week. In the second post-treatment week the survivors recovered gradually and looked quite healthy again at the end of the observation period. The individual body weight of the survivors on day 7, revealed growth retardation or weight loss. On day 14 the body weight of most of the rats in the higher dose groups were still lower or only slightly higher than the initial weight. Macroscopic examination at autopsy of the rats that died on the first few post-treatment days revealed blood-stained urine in the bladder of all rats. In the rats that died thereafter and in those that survived the observation period no treatment-related gross alterations were found. Deaths occurred between 18 hours and 9 days after treatment. The oral LD50 of the test substance was found to be 797 mg/kg bw with 703 and 905 as the 95% confidence limits.

In a second acute oral toxicity study (1977) is available. The test substance was administered by gavage in single doses of 100, 215, and 464 mg/kg bw to groups of 5 female SD rats and the animals were observed for 7 days. Deaths occurred within 5 days after dosage. The oral LD50 of the test substance was found to be 271 mg/kg bw with 200 and 369 as the 95% confidence limits.

One klimisch 4 study is available in which a LD50 of 1700 mg/kg bw is reported.

Acute dermal toxicity

In an acute dermal toxicity study (1977) the test substance was administered undiluted in doses of 464, 1000, 2150, 4640, 10000 mg/kg bw to groups of 5 female SD rats and the animals were observed for 7 days. Deaths occurred within 7 days after dosage. The oral LD50 of the test substance was found to be > 10000 mg/kg bw.

One klimisch 4 study is available in which a LD50 of >5000 mg/kg bw is reported.

Justification for classification or non-classification

The test substance has to be classified for acute oral toxicity as Acute Toxicity 4: H302: harmful if swallowed according to Regulation (EC) No 1272/2008.

The test substance does not have to be classified for acute dermal toxicity according to Regulation (EC) No 1272/2008.