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Description of key information

Oral LD50 estimated to be greater than 300 mg/kg bw (Wistar rat, equivalent to EU Method B.1, non GLP)

Dermal LD50 estimated to be greater than 1000 mg/kg bw (Wistar rat, equivalent to EU Method B.4, non GLP)

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:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
Not provided
Route of administration:
oral: gavage
Vehicle:
other: carboxymethyl cellulose
Details on oral exposure:
VEHICLE
- Test substance was administered as solution in 1% carboxymethyl cellulose
- Concentration in vehicle: not specified
- Amount of vehicle (if gavage): not specified
Doses:
300 mg/kg bw
No. of animals per sex per dose:
Three
Control animals:
no
Details on study design:
Clinical signs and bodyweight development were monitored during the study over a period of up to 7 days.
Mortality:
One animal was killed for humane reasons, approximately four hours after dosing due to the occurrence of severe clinical signs.
Clinical signs:
Ataxia and hunched posture were noted in all animals during the day of dosing. Ptosis and dark red stained urine was also noted in one animal and noisy respiration was also noted in one other animal.
Body weight:
Surviving animals showed expected gains in bodyweight.
Gross pathology:
Abnormalities noted at necropsy of the animal that was humanely killed were dark liver, dark kidneys, raised limiting ridge in the stomach, reddened non-glandular epithelium of the stomach and pale red coloured fluid filled bladder. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Table 1: Clinical signs observed during the study

Dose level mg/kg

Animal number and sex

Effects noted after dosing (hours)

Effects noted during period after dosing (days)

0.5

1

2

4

1

2

3

4

5

6

7

300

1-0

Female

HARn

HARn

HA

HA

0

0

0

0

0

0

0

1-1

Female

HA

HA

HA

HA

0

0

0

0

0

0

0

1-2

Female

HA

HA

APtU

APtUX*

 

 

 

 

 

 

 

0 = no signs of systemic toxicity; H = Huntched posture; A = Ataxia; Pt = Ptosis; U = Dark red stained urine; Rn = Noisy respiration; X* Animal killed for humane reasons due to the occurrence of severe clinical signs of toxicity

Table 2: Bodyweight information

Dose level mg/kg

Animal number and sex

Bodyweight (g)

Bodyweight (g) at death

Bodyweight gain (g) day 0 to day 7

Day -1

Day 0 (day of dosing)

Day 7

300

1-0

Female

158

152

161

 

9

1-1

Female

167

159

167

 

8

1-2

Female

166

157

-

152

-

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Based on the results of the study, the oral LD50 of the substance in the rat was estimated to be greater than 300 mg/kg bw.
Executive summary:

The acute oral toxicity of the substance was tested on three female rats of the Wistar strain by administering a single oral dose of 300 mg/kg bodyweight in 1% carboxymethyl cellulose by gavage. The study was not conducted under GLP, but followed the basic principles of the standard acute method as laid down in EU Method B.1. Ataxia and huntched posture were observed in all animals following oral administration. Noisy respiration was also observed in one animal after dosing. One animal showed severe signs of systemic toxicity on the day of dosing, including ptosis and dark red stained urine. This animal was killed for humane reasons, approximately four hours after dosing. During necropsy a number of abnormalities were observed for this animal, including dark liver, dark kidneys, raised limiting ridge in the stomach, reddened non-glandular epithelium of the stomach and pale red coloured fluid filled bladder. No abnormalities were noted at necropsy of the other two animals that were killed at the end of the study. These two animals were also gaining bodyweights as expected. Based on the study it was estimated that the oral LD50 value for the substance in the rat was greater than 300 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
300 mg/kg bw
Quality of whole database:
Poorly documented, non-GLP study following principles of relevant EU Method

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:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
Not reported
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Not reported
Duration of exposure:
24 hours
Doses:
1000 mg/kg bw
No. of animals per sex per dose:
Three
Control animals:
no
Details on study design:
Clinical signs and bodyweight development as well as signs of skin irritation were monitored during the study over a period of eight days. All animals were subjected to gross necropsy.
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted.
Body weight:
Individual bodyweights developed as expected.
Gross pathology:
No abnormalities were observed during necropsy.
Other findings:
Weak signs of dermal irritation noted were very slight erythema, glossy skin, small superficial scattered scabs and scab lifting to reveal glossy skin.

Table 1: Individual dermal reactions, as scored according to Draize system

Dose level mg/kg

Animal number and sex

Observation

Effects noted after initiation of exposure (days)

1

2

3

4

5

6

7

8

1000

1-0 female

Erythema

1

1

0

1

1

1

1

0

Oedema

0

0

0

0

0

0

0

0

Other

0

0

G

GSs

GSs

Ss

Ss

Ss

1-1 female

Erythema

1

1

1

1

1

1

0

0

Oedema

0

0

0

0

0

0

0

0

Other

0

0

GSs

GSs

GSs

GSs

GSs

GSs

1-2 female

Erythema

1

1

1

1

1

1

0

0

Oedema

0

0

0

0

0

0

0

0

Other

0

0

Ss

Ss

Ss

Ss

Ss

SsSg

0 = no reaction; G = Glossy skin; Ss = Small superficial scattered scabs; Sg = Scab lifting to reveal glossy skin

Table 2: Individual bodyweights and bodyweight changes

Dose level mg/kg

Animal number and sex

Bodyweight (g) at day

Bodyweight change (g)

 

 

1000

1-0 female

212

216

4

1-1 female

212

221

9

1-2 female

208

216

8

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Based on the results of the study, the dermal LD50 in the rat was found to be greater than 1000 mg/kg bw.
Executive summary:

The acute dermal toxicity of the substance was tested on three female rats of the Wistar strain by applying the undiluted substance at a dose of 1000 mg/kg bw to the intact skin under semi-occlusion for a period of 24 hours. The study was not conducted under GLP, but followed the basic principles of the standard acute method as laid down in EU Method B.4. No deaths occured. No clinical symptoms or signs of systemic toxicity were observed following dermal exposure. No abnormalities were noted at necropsy of the animals that were killed at the end of the study. All animals were also gaining bodyweights as expected. Only weak signs of dermal irritation were observed. Based on the study it was estimated that the dermal LD50 value for the substance in the rat was greater than 1000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
1 000 mg/kg bw
Quality of whole database:
Poorly documented, non-GLP study following principles of relevant EU Method

Additional information

Justification for classification or non-classification

On the basis of the available data generated in poorly documented, non-GLP screening studies following the principles of the relevant EU Methods, it is proposed to apply the following classification of the substance in accordance with CLP Regulation (EC) No. 12727/2008:

- Oral exposure route: Acute Tox. Cat. 4

- Dermal exposure route: Acute Tox. Cat. 4

- Inhalation exposure route: Acute Tox. Cat. 3

No study on the acute inhalation toxicity of the substance was conducted. The acute inhalation hazard of the substance can be predicted by route-to-route extrapolation with the GESAMP acute inhalation extrapolation method described by Höfer et al. (2011). Using the proposed system for classification (see Table 1 and Table 2 in the appendix), hazard ratings of 1 for acute oral toxicity, 1 for acute dermal toxicity and 1 for skin irritation may be assumed for the substance. This hazard rating results in an estimated acute inhalation toxicity rating of 2, associated with an ATE/LC50 inhalation of >2 to ≤10 mg/L. Such an ATE corresponds to a GHS classification into “Acute Tox. Cat. 3”. ( Höfer T, James D, Syversen T, Bowmer T. 2011. Estimation of the acute inhalation hazards of chemicals based on route-to-route and local endpoint extrapolation: experience from bulk maritime transport. Alternatives to Laboratory Animals (ATLA) 39, 541-556.)

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