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Description of key information

Acute Oral Toxicity

Under the conditions of this study, the oral LD50 value for the test material (50 % in corn oil) was 14.9 g/kg in both male and female rats.

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:
15 September 1976 to 06 October 1976
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 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Remarks:
The study pre-dates the inception of GLP
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Albino
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: Young adult
- Weight at study initiation: 200 to 300 grams
- Fasting period before study: Yes, fasted for 24 hours
- Housing: In common cages with other rats on the same dosage level
- Diet: ad libitum
- Water: ad libitum
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50 % w/w in corn oil
Doses:
2.0, 4.0, 8.0, 16.0, 32.0 and 64.0 g/kg
No. of animals per sex per dose:
5 animals per dose. Not specified as to how many males and females per dose level; rats were assigned to various dose levels at random with both sexes being equally distributed.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Daily
- Necropsy of survivors performed: No
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
14 900 mg/kg bw
Based on:
test mat.
95% CL:
>= 9 600 - <= 23 000
Mortality:
No deaths were observed at the 2.0 and 4.0 g/kg dose levels. One death was observed at the 8.0 g/kg dose level, 2 deaths were observed at the 16.0 g/kg dose level and 5 deaths were observed at both the 32.0 and 64.0 g/kg dose levels.
Clinical signs:
At the 2.0 g/kg dose level, no toxic effects were noted. At the 4.0 g/kg dose level nasal haemorrhage was evident for 24 hours. At the 8.0 and 16.0 g/kg dose levels, nasal haemorrhage was accompanied with wet, oily coats. Slight diarrhoea was noted at the 16.0 g/kg dose level. The animals dosed at 32.0 g/kg were languid, exhibiting nasal haemorrhage, diarrhoea and wet, oily, unkempt coats.
For the animals dosed at 64.0g/kg, observations included lethargy, nasal and ocular haemorrhage, diarrhoea, wet, oily coats and generally emaciated condition.
Other findings:
The test material was equally toxic to males and females.

Table 1: Sumary of Mortality Data

Group No.

No. of animals

Dose level (g/kg)

Number and Day of Deaths

Total

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Survived

Died

I

5

2.0

 

 

 

 

 

 

 

 

 

 

 

 

 

 

5

II

5

4.0

 

 

 

 

 

 

 

 

 

 

 

 

 

 

5

III

5

8.0

 

 

 

 

 

1

 

 

 

 

 

 

 

 

4

1

IV

5

16.0

 

 

 

 

 

2

 

 

 

 

 

 

 

 

3

2

V

5

32.0

 

 

 

2

2

 

 

1

 

 

 

 

 

 

0

5

VI

5

64.0

 

1

1

3

 

 

 

 

 

 

 

 

 

 

0

5

Interpretation of results:
other: Not classified in accordance with EU criteria
Conclusions:
Under the conditions of this study, the LD50 was determined to be 14.9 g/kg in the rat.
Executive summary:

The acute oral toxicity of the test material was investigated using methodology similar to the standardised guideline OECD 401.

A group of 30 albino male and female rats were employed to the study to establish an LD50 range for the test material. Fasted animals were dosed by gavage at 2.0, 4.0, 8.0, 16.0, 32.0 and 64 g/kg with the test material at 50 % in corn oil. The test animals were assigned to various dose levels at random; both sexes were distributed equally. After the test material had been administered animals were observed daily for 14 days.

No deaths were observed at the 2.0 and 4.0 g/kg dose levels. One death was observed at the 8.0 g/kg dose level, 2 deaths were observed at the 16.0 g/kg dose level and 5 deaths were observed at both the 32.0 and 64.0 g/kg dose levels.

At the 2.0 g/kg dose level, no toxic effects were noted. At the 4.0 g/kg dose level nasal haemorrhage was evident for 24 hours. At the 8.0 and 16.0 g/kg dose levels, nasal haemorrhage was accompanied with wet, oily coats. Slight diarrhoea was noted at the 16.0 g/kg dose level. The animals dosed at 32.0 g/kg were languid, exhibiting nasal haemorrhage, diarrhoea and wet, oily, unkempt coats.

For the animals dosed at 64.0g/kg, observations included lethargy, nasal and ocular haemorrhage, diarrhoea, wet, oily coats and generally emaciated condition.

Under the conditions of this study, the oral LD50 value for the test material was 14.9 g/kg in both male and female rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
14 900 mg/kg bw
Quality of whole database:
Two studies are available to address this endpoint, one key and one supporting. The studies were conducted prior to the inception of GLP though are considered to be adequate for risk assessment purposes. The key information is included in the reports. The quality of the database is therefore considered to be good.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute Oral Toxicity

In the key study, the acute oral toxicity of the test material was investigated using methodology similar to the standardised guideline OECD 401.

A group of 30 albino male and female rats were employed to the study to establish an LD50 range for the test material. Fasted animals were dosed by gavage at 2.0, 4.0, 8.0, 16.0, 32.0 and 64 g/kg with the test material at 50 % in corn oil. The test animals were assigned to various dose levels at random; both sexes were distributed equally. After the test material had been administered animals were observed daily for 14 days.

No deaths were observed at the 2.0 and 4.0 g/kg dose levels. One death was observed at the 8.0 g/kg dose level, 2 deaths were observed at the 16.0 g/kg dose level and 5 deaths were observed at both the 32.0 and 64.0 g/kg dose levels.

At the 2.0 g/kg dose level, no toxic effects were noted. At the 4.0 g/kg dose level nasal haemorrhage was evident for 24 hours. At the 8.0 and 16.0 g/kg dose levels, nasal haemorrhage was accompanied with wet, oily coats. Slight diarrhoea was noted at the 16.0 g/kg dose level. The animals dosed at 32.0 g/kg were languid, exhibiting nasal haemorrhage, diarrhoea and wet, oily, unkempt coats.

For the animals dosed at 64.0g/kg, observations included lethargy, nasal and ocular haemorrhage, diarrhoea, wet, oily coats and generally emaciated condition.

Under the conditions of this study, the oral LD50 value for the test material was 14.9 g/kg in both male and female rats.

In the supporting study, the acute oral toxicity of the test material was investigated using methodology similar to the standardised guideline OECD 401.

A group of 30 albino male and female rats were employed to the study to establish an LD50 range for the test material. Fasted animals were dosed by gavage at 2.0, 4.0, 8.0, 16.0, 32.0 and 64 cm3/kg with the test material at 5 % in corn oil. The test animals were assigned to various dose levels at random; both sexes were distributed equally. After the test material had been administered animals were observed daily for 14 days.

At the 2.0, 4.0, 8.0, 16.0 and 32.0 cm3/kg concentrations there were no deaths; at 64.0 cm3/kg, there were two deaths. At 16 .0 cm3/kg and below, animals did not exhibit any toxic effects. At 32.0 cm3/kg animals exhibited mild diarrhoea and ruffled and wet coats. Normalcy prevailed within 72 hours. At the 64.0 cm3/kg dose level, slight ocular haemorrhage and moderate diarrhoea for 48-72 hours following forced feeding and excessive lacrimation were noted. Coats were wet and unkempt for 72-96 hours post dosing; survivors returned to normal within 96 hours.

Under the conditions of this study, the LD50 was determined to be in excess of 64.0 cm3/kg.

Read-across to structurally similar substance (Acute oral toxicity)

The acute oral toxicity of the test material was investigated in accordance with the standardised guidelines OECD 401 and EU Method B1. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

A group of 5 male and 5 female rats was exposed to the test material in corn oil at a limit dose of 2000 mg/kg bw. Fasted animals were dosed via a syringe and plastic catheter. All animals were observed for 14 days after dosing before being terminated on day 15 and subjected to macroscopic examination at necropsy.

There were no cases of mortality during the study. Signs of reaction to treatment observed shortly after dosing in all animals were pilo-erection, abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy and pallor of extremities. Recovery, as judged by external appearance and behaviour, was advanced by Day 2 and complete by Day 3. Terminal autopsy findings were normal.

Under the conditions of this study the acute lethal oral dose was found to be greater than 2000 mg/kg bodyweight.

Inhalation Toxicity

In accordance with section 8.5.2 of Column 2 of REACH Annex VIII, testing via the inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size. For the test material, exposure via the inhalation route is unlikely and it is therefore considered justified to omit this study.

Dermal Toxicity

In accordance with column 2 of section 8.5.3 of REACH, the acute dermal toxicity study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation).

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to acute toxicity via the oral route.

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