Registration Dossier

Administrative data

Description of key information

The test substance was assessed for acute oral toxicity in rats using a single dose administered by oral gavage.  The LD50 was calculated to be 2.66 mL/kg bw with 95% confidence limits of 2.43 and 2.9 mL/kg bw.
The test substance was assessed for acute dermal toxicity in New Zealand white rabbits. There were no treatment-related deaths therefore the LD50 was > 5000 mg/kg.
Supporting information was available on the analogue substance Florhydral. An acute dermal toxicity study was performed on rats using a fixed dose procedure. The LD50 was > 5000 mg/kg for Florhydral. A further acute dermal study was performed on rabbits also using a fixed dose procedure. In this study on the analogue substance, Florhydral, the LD50 was > 5000 mg/kg.

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:
1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards with acceptable restrictions.
Qualifier:
no guideline followed
Principles of method if other than guideline:
The test substance was administered to male and female rats by gavage in single doses of 2.4, 2.9, 3.2 or 4.2 mL per kg bw. After treatment the rats received stock diet and tap water ad libitum. They were observed for signs of intoxication during a 14 day period, after wich autopsies were carried out on survivors and the LD 50 was calculated.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Central Institute for the Breeding of Laboratory Animals TNO, Zeist, Netherlands.
- Age at study initiation: Young adult, age not specified.
- Weight at study initiation: Males 200 to 260 g, females from 100 to 134 g.
- Fasting period before study: Overnight
- Diet (e.g. ad libitum): Stock diet available ad libitum
- Water (e.g. ad libitum): Ad libitum
- Housing: In groups of 5 in stainless-steel cages with grid-bottom and front.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 1 °C
- Air changes (per hr): Well ventilated, but air changes not specified.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
2.4, 2.9, 3.5 or 4.2 mL/kg bw
No. of animals per sex per dose:
Five/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Other examinations performed: Observed for signs of intoxication.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2.66 mL/kg bw
Based on:
test mat.
95% CL:
2.43 - 2.91
Mortality:
Deaths occurred between 7 h and 3 days after dosing. Then the survivors recovered gradually and looked quite healthy at the end of the observation period.
Clinical signs:
Within a few hours after treatment the rats showed sedation and signs of ataxia. Later, signs of emaciation, encrustations around eyes and nostrils and coma were frequently observed.
Gross pathology:
Macroscopic examination of the survivors did not reveal any treatment-related gross alterations.

Doses applied and mortality figures:

Dose (mL/kg)

Mortality

Number

Percent

Males

Females

2.4

2/5

1/5

30

2.9

3/5

4/5

70

3.5

4/5

5/5

90

4.2

5/5

5/5

100

Conclusions:
The test substance was assessed for acute oral toxicity in rats using a single dose administered by oral gavage. The LD50 was calculated to be 2.66 mL/kg bw with 95% confidence limits of 2.43 and 2.9 mL/kg bw.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 550 mg/kg bw

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
Study period:
3rd July 1980 to 1st August 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions.
Qualifier:
no guideline followed
Principles of method if other than guideline:
The test substance was applied once to the clipped skin of New Zealand white rabbits at 5 g/kg over approximately 10 % of the body surface. Abrasions were made in half of the rabbits and extended the length of the exposure site, scratching only the strarum corneum, but did not reach the derma or produce bleeding. The area was covered with an occlusive dressing for 24 h after which the wrapping was removed and the exposed area was wiped, but not washed, to remove excess material. Dermal reactions were scored at 1, 7 and 14 days according to Draize. The rabbtis were observed daily for 14 days for signs of toxicity, pharmacological effects and mortality. All animals were examined for gross pathology at termiantion.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Perfection Breeders, Nicholas Helf
- Age at study initiation: approximately 8 weeks old
- Weight at study initiation: 2.3 - 2.6 kg
- Housing: 2/ cage in suspended wire mesh cages
- Diet (e.g. ad libitum): Purina rabbit chow ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least 1 week
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Back
- % coverage: 10 %
- Type of wrap if used: Gaize patches secured with adhesive tape and the trunks were wrapped with impervious material.

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

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5 g/kg. The dose was based on the sample weight as calculated from the specific gravity.
- Constant volume or concentration used: No, volume ranged from 12.2 to 13.8 cc.
- For solids, paste formed: Not applicable, test material is a liquid
Duration of exposure:
Single exposure; the test material was not removed.
Doses:
5 g/kg
No. of animals per sex per dose:
6 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 1, 7 and 14 days. The rabbits were scored daily for 14 days for signs of toxicity, pharmacological effects and mortality. Bodyweights were recorded pre-test and in the survivors at 14 days.
- Necropsy of survivors performed: Yes, all animals were examined for gross pathology.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 other: g/kg
Based on:
test mat.
Mortality:
There was one death at Day 4.
Clinical signs:
In the rabbit that died, pre-death toxic signs were diarrhoea, tachypnea, prostration, flaccid muscle tone and spasm.
Toxic sings in survivors included lethargy and diarrhoea.
Slight to moderate erythema was noted on Days 1 and 7 and was absent or slight on Day 14.
Body weight:
There was a slight loss in body weight in 4 out of 5 surviving animals.
Gross pathology:
Necropsy findings of survivors were normal. The spontaneous death had lung abnormalities.
Conclusions:
The test substance was assessed for acute dermal toxicity in New Zealand white rabbits. There were no treatment-related deaths therefore the LD50 was > 5.0 g/kg.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Additional information

Acute oral toxicity

The test substance was assessed for acute oral toxicity in rats using a single dose administered by oral gavage. The LD50 was calculated to be 2.66 mL/kg bw with 95% confidence limits of 2.43 and 2.9 mL/kg bw. (density = 0.959 g/ml) = 2550 mg/kg bw which is above the level for classification according to CLP (2000 mg/kg bw).

Acute inhalation toxicity

No study was avaliable.

Acute dermal toxicity

The test substance was assessed for acute dermal toxicity in New Zealand white rabbits. There were no treatment-related deaths therefore the LD50 was > 5000 mg/kg.

Supporting information was available on the analogue substance Florhydral. An acute dermal toxicity study was performed on rats using a fixed dose procedure. The LD50 was > 5000 mg/kg for Florhydral. A further acute dermal study was performed on rabbits also using a fixed dose procedure. In this study on the analogue substance, Florhydral, the LD50 was > 5000 mg/kg.

To support toxicological endpoints as part of the REACH registration of Bourgeonal (Target substance) it is proposed to read across to Florhydral (Source substance). The use of read-across works within the spirit of REACH, and the stated aim of the legislation to reduce animal testing where possible. The Target Substance and Source Substance have been characterised in using the categories and databases present in the OECD QSAR toolbox. From the profile, it can be seen that the two substances share structural similarities and also ‘mechanistic action’ similarities which are both general and endpoint specific. Therefore read across is justified.


Justification for selection of acute toxicity – oral endpoint
The sudy was performed on the target substance using standard methodology. 2.66 ml/kg bw (density = 0.959 g/ml) = 2550 mg/kg bw

Justification for selection of acute toxicity – dermal endpoint
The sudy was performed on the target substance using standard methodology.

Justification for classification or non-classification

Based on the oral LD50 values of 2550 mg/kg bodyweight and dermal LD50 values of > 5000 mg/kg bodyweight, there is no need to classify Bourgeonal for acute to toxicity in accordance with the criteria outlined in Annex VI of 67/548/EEC (DSD) and Annex I of 1272/2008/EC (CLP).