Registration Dossier

Administrative data

Description of key information

Oral: LD50= > 5000 mg/kg bw, male rat, equiv. to OECD 401, Moreno 1980
Dermal: LD50= > 2000 mg/kg bw, male/female rabbit, equiv. to OECD 402, Moreno 1979

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:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Pre-GLP but the method followed is similar to a recognised guideline; limited test material characeterisation.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Recognised animal supplier
- Age at study initiation: 8 weeks
- Weight at study initiation: 198-235g
- Fasting period before study: not reported
- Housing: housed 5 per cage in suspended wire mesh cages
- Diet (e.g. ad libitum): Rat chow ad libitum except for 16-20 hours prior to dosing.
- Water (e.g. ad libitum): ad libitum except for 16-20 hours prior to dosing.
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The test material was given orally by syringe and 13 gauge blunt end needle. One group of ten male rats were dosed at 5g/kg of body weight. For liquid materials, the dose was based on the sample weight as calculated from the specific gravity. The vehicle, if any, was chosen because of its lack of known toxicity, lack of physiological effect and because it is relatively unreactive with other chemical substances.
Doses:
5g/kg
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were observed 3-4 hours after dosing and once daily for 14 days.
- Necropsy of survivors performed: no
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
act. ingr.
Mortality:
All animals survived.
Clinical signs:
Lethargy was noted in five or more animals 3-4 hours post dose. Isolated instances of prostration, diarrhea, eyes bulging, and chromorhinorrhea were also noted 3-4 hours post dose. One instance of chromorhinorrhea was noted on Day 1. All animals were normal on Days 2 thru 5. One instance of lethargy was noted on Day 6. All animals were normal on Days 7 and 8. Isolated instance of chromorhinorrhea was noted on Days 9 and 10. All animals were normal on Days 11 and 12. An isolated instance of chromorhinorrhea was noted on Day 1 Isolated instances of lethargy, piloerection, and ptosis were noted on Day 14.
Body weight:
Not measured
Gross pathology:
Not measured
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The acute oral median lethal dose (LD50) of the test material in male Wistar rats was estimated to be greater than 5000 mg/kg body weight.
Executive summary:

The study was performed to assess the acute oral toxicity of the test material in the Wistar strain of rat. The study was performed pre-GLP and followed a method equivalent to OECD guideline 401. The test material was administered orally, after fasting for 16 -20 hours, once only by gavage. 10 male test animals were dosed at 5000 mg/kg body weight. Mortality and clinical signs were monitored during the study. All animals were not subjected to gross necropsy after an observation period of 14 days. There were no deaths but lethargy was noted in five or more animals 3-4 hours post dose. Isolated instances of prostration, diarrhea, eyes bulging, and chromorhinorrhea were also noted 3-4 hours post dose. One instance of chromorhinorrhea was noted on Day 1. All animals were normal on Days 2 through to 5. One instance of lethargy was noted on Day 6. All animals were normal on Days 7 and 8. Isolated instance of chromorhinorrhea was noted on Days 9 and 10. All animals were normal on Days 11 and 12. An isolated instance of chromorhinorrhea was noted on Day 1 Isolated instances of lethargy, piloerection, and ptosis were noted on Day 14. The acute oral median lethal dose (LD50) of the test material in the male Wistar strain rat was estimated to be greater than 5000 mg/kg bodyweight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
The available information as a whole meets the tonnage driven information requirements of REACH. The substance shows no evidence of acute toxicity by the oral or dermal routes.

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:
weight of evidence
Study period:
1979
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Pre-GLP study following a method equivalent to a recognised guideline; limited test material characeterisation.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Recognised animal supplier
- Age at study initiation: at least 8 weeks old.
- Weight at study initiation: not reported
- Housing: The animals were housed 2/cage in suspended wire mesh cages.
- Diet: Rabbit chow ad libitum
- Water: ad libitum
- Acclimation period: One week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: abdomen
- Type of wrap if used: The test material was applied once dermally to the prepared site under gauze patches. The patches were secured with adhesive tape and the trunks were wrapped with impervious material.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the exposure site was wiped, but not washed, to remove excess material.
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 g/kg
Duration of exposure:
24h
Doses:
2000 mg/kg
No. of animals per sex per dose:
8 males and 2 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Dermal reactions were scored at 24 hours by the Draize scoring system. The rabbits were .observed da1ly for 14 days for signs of toxicity, pharmacological effects and mortality. Body weights were recorded pretest and in survivors at 14 days.
pretest anp in the .·survivors at 14 days.
- Necropsy of survivors performed: no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One animal died on day 4
Clinical signs:
Pre-death toxic signs included lethargy and diarrhea. Diarrhea was noted in 5 animals. Isolated instances of yellow nasal discharge, lethargy, and ptosis were occasionally noted in 3 animals. Three out of nine surviving animals remained normal throughout the observation period.
Body weight:
no significant changes observed.
Gross pathology:
not examined
Other findings:
Very slight to well defined erythema and very slight to slight edema were noted at 24 hours.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study the LD50 was determined to be > 2000 mg/kg and so the test material is not considerd to be toxic to New Zealand rabbits via the dermal route.
Executive summary:

The study was performed to assess the dermal toxcity of the test material to New Zealand White rabbit. The study was performed pre-GLP and followed a method similar to OECD 402 guideline. The test substance was evaluated in 10 New Zealand white rabbits. A dose of 2000 mg/kg test substance (undiluted), was applied to intact and abraded clipped skin site under a occlusive dressing for 24 hours. Skin observations were made 24 hours after patch removal and then daily for 14 days for signs of toxicity, pharmacological effects and mortality. One test animal died on day four; pre-death toxic signs included lethargy and diarrhea. Diarrhea was noted in 5 animals. Isolated instances of yellow nasal discharge, lethargy, and ptosis were occasionally noted in 3 animals. Three out of nine surviving animals remained normal throughout the observation period. Very slight to well defined erythema and very slight to slight edema were noted at 24 hours. Under the conditions of this study the LD50 is considered to be greater than 2000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The available information as a whole meets the tonnage driven information requirements of REACH.

Additional information

Acute Oral:

The study was performed to assess the acute oral toxicity of the test material in the Wistar strain of rat. The study was performed pre-GLP and followed a method equivalent to OECD guideline 401. The test material was administered orally, after fasting for 16 -20 hours, once only by gavage. 10 male test animals were dosed at 5000 mg/kg body weight. Mortality and clinical signs were monitored during the study. All animals were not subjected to gross necropsy after an observation period of 14 days. There were no deaths but lethargy was noted in five or more animals 3-4 hours post dose. Isolated instances of prostration, diarrhea, eyes bulging, and chromorhinorrhea were also noted 3-4 hours post dose. One instance of chromorhinorrhea was noted on Day 1. All animals were normal on Days 2 through to 5. One instance of lethargy was noted on Day 6. All animals were normal on Days 7 and 8. Isolated instance of chromorhinorrhea was noted on Days 9 and 10. All animals were normal on Days 11 and 12. An isolated instance of chromorhinorrhea was noted on Day 1 Isolated instances of lethargy, piloerection, and ptosis were noted on Day 14. The acute oral median lethal dose (LD50) of the test material in the male Wistar strain rat was estimated to be greater than 5000 mg/kg bodyweight.

 

Acute Dermal:

The study was performed to assess the dermal toxcity of the test material to New Zealand White rabbit. The study was performed pre-GLP and followed a method similar to OECD 402 guideline. The test substance was evaluated in 10 New Zealand white rabbits. A dose of 2000 mg/kg test substance (undiluted), was applied to intact and abraded clipped skin site under a occlusive dressing for 24 hours. Skin observations were made 24 hours after patch removal and then daily for 14 days for signs of toxicity, pharmacological effects and mortality. One test animal died on day four; pre-death toxic signs included lethargy and diarrhea. Diarrhea was noted in 5 animals. Isolated instances of yellow nasal discharge, lethargy, and ptosis were occasionally noted in 3 animals. Three out of nine surviving animals remained normal throughout the observation period. Very slight to well defined erythema and very slight to slight edema were noted at 24 hours. Under the conditions of this study the LD50 is considered to be greater than 2000 mg/kg.


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

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

Justification for classification or non-classification

The substance does not meet classification criteria under EU Directive 67/548/EEC for acute toxicity.

The substance does not meet classification criteria under Regulation (EC) No 1272/2008 for acute toxicity.