Registration Dossier

Administrative data

Description of key information

Acute toxicity: oral: LD50 > 5000 mg/kg bw (similar to OECD 401, K, rel. 2).
Acute toxicity: dermal: LD50 > 2000 mg/kg bw (similar to OECD 402, K, rel. 2).

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:
From June 14 to June 28, 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study comparable to OECD test guideline No. 401 but GLP status not reported.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
other: Section 1500.3 - Federal Hazardous Substances Act Regulations - 16 CFR
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace Animals, Inc., Boyertown, PA.
- Age at study initiation: no data
- Weight at study initiation: 200-300 g
- Fasting period before study: overnight deprivation of food
- Housing: 5 rats/cage by sex, in stainless steel cages with elevated wire mesh flooring
- Diet (e.g. ad libitum): Wayne Lab-Blox ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: appropriate time

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-23
- Humidity (%): 45-55
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: no data
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
None
Doses:
5000 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: frequently on the day of dosage, and twice per day thereafter.
- Frequency of weighing: on the day of dosage (individually), and on Day 7 and 14 after dosing (grouped)
- Necropsy of survivors performed: yes, gross examinations
Statistics:
none
Preliminary study:
not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality
Clinical signs:
All animals appeared normal throughout the 14 day observation period
Body weight:
All animals gained weight
Gross pathology:
No gross abnormalities
Other findings:
None

None

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Oral LD50Combined > 5000 mg/kg bw
Executive summary:

In a limit acute oral toxicity study performed similarly to the OECD test guideline No. 401, a group of fasted, Sprague-Dawley rats (5/sex) was administered a single oral dose of undiluted test material at 5000 mg/kg bw by gavage. The animals were observed for mortality, clinical signs and body weight for 14 days and then necropsied for macroscopic observations.

No mortality and no clinical signs were observed throughout the study. There was no adverse effect on bodyweight gain. No gross abnormalities were observed at necropsy.

 

Oral LD50Combined > 5000 mg/kg bw

 

Under the test conditions, the test material is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP).

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
The key study is of good quality (Klimisch score = 2) although GLP status is not reported.

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:
From June 15 to June 29, 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study comparable to OECD test guideline No. 402 with deviations not affecting the integrity of the result. Indeed, only 6 animals were tested instead of the 10 required by the OECD Test Guideline No. 402 for a limit test. However having 4 more animals would not impact the LD50 value since no mortality occurred within this study. Moreover half of the animals had abraded skin which improved skin permeability, and therefore absorption. GLP status not reported.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
other: Section 1500.4 - Federal Hazardous Substance Act Regulation - 16 CFR
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Limit test using 6 animals instead of 10, half of them having abraded skin
Principles of method if other than guideline:
Not applicable
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace Animals, Inc., Boyertown, PA.
- Age at study initiation: no data
- Weight at study initiation: 2.3-3.0 kg bw.
- Fasting period before study: no.
- Housing: individually, in stainless steel cages with elevated wire mesh flooring.
- Diet (e.g. ad libitum): Wayne 15% Rabbit ration ad libitum.
- Water (e.g. ad libitum): tap water ad libitum.
- Acclimation period: appropriate time.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15.5 - 23
- Humidity (%): 40-45
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: no data
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: backs (clipped skin, 3 with abraded skin).
- % coverage: approximately 10%.
- Type of wrap if used: large gauze patches, impervious material wrapped snugly around the trunk.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no (wiping only)
- Time after start of exposure: 24 hours.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.0 g/kg bw.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations (systemic and topical): frequently during the first day, and twice per day thereafter (morning and afternoon).
- Frequency of weighting: on the day of dosage, weekly thereafter, and prior to sacrifice.
- Necropsy of survivors performed: yes (gross necropsy)
Statistics:
None
Preliminary study:
Not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
None.
Body weight:
A loss of body weight was noted for 1/3 female at 7 days.
Gross pathology:
No gross abnormalities were noted.
Other findings:
Mild erythema and severe oedema were observed after unwrapping at 24 hours. Eschar was noted for all animals by day 4 which was still evident at 14 days.

None

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Dermal LD50Combined > 2000 mg/kg bw
Executive summary:

In a limit acute dermal toxicity study performed similarly to the OECD test guideline No. 402, New Zealand White rabbits (3/sex) were occlusively exposed to undiluted test material for 24 hours at dose of 2000 mg/kg bw. The animals were observed for mortality, clinical signs including dermal reactions and body weight for 14 days and then necropsied for macroscopic observations.

No mortality and no clinical signs were observed during the study. A loss of body weight was noted for 1/3 female at 7 days.

Mild erythema and severe oedema were observed after unwrapping at 24 hours. Eschar was noted for all animals by day 4 which was still evident at 14 days.

Dermal LD50Combined > 2000 mg/kg bw.

Under the test conditions, the test material is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP).

This study is considered as acceptable and satisfies the requirement for acute dermal toxicity endpoint.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The key study is of good quality (Klimisch score = 2) although GLP status is not reported. Deviations do not affect the integrity of the result.

Additional information

Acute toxicity via oral route:

A key study was identified (Biosearch Inc., 1984). In this limit acute oral toxicity study performed similarly to the OECD test guideline No. 401, rats (5/sex) were administered a single oral dose of undiluted test material at 5000 mg/kg bw by gavage. No mortality and no clinical signs were observed throughout the study. There was no adverse effect on bodyweight gain. No gross abnormalities were observed at necropsy.

Oral LD50Combined > 5000 mg/kg bw.

Acute toxicity via dermal route:

A key study was identified (Biosearch Inc., 1984). In this limit acute dermal toxicity study performed similarly to the OECD test guideline No. 402, rabbits (3/sex, half clipped and half abraded)were occlusively exposed to undiluted test material for 24 hours at dose of 2000 mg/kg bw. No mortality and no clinical signs were observed during the study. A loss of body weight was noted for 1/3 female at 7 days. Mild erythema and severe oedema were observed after unwrapping at 24 hours. Eschar was noted for all animals by day 4 which was still evident at 14 days.

Dermal LD50Combined > 2000 mg/kg bw.


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

Justification for selection of acute toxicity – inhalation endpoint
Not required for substances at the REACH Annex VII tonnage level.

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

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008 including ATP6.

Self-classification:

Acute toxicity (Oral):

Based on the available information, the substance is not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) as the oral LD50 is higher than 5000 mg/kg bw.

Acute toxicity (Dermal):

Based on the available information, the substance is not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) as the dermal LD50 is higher than 2000 mg/kg bw.

Acute toxicity (Inhalation):

No information was available.

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the Annex VI of the Regulation (EC) No. 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value, oral for a Category 1 classification (C ≤ 300 mg/kg bw) and at the guidance value, oral for a Category 2 classification (2000 mg/kg bw ≥ C > 300 mg/kg bw). No classification required.

Specific target organ toxicity: single exposure (Dermal):

The classification criteria according to the Annex VI of the Regulation (EC) No 1272/2008 as specific target organ toxicant (STOT) – single exposure, dermal are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value, dermal for a Category 1 classification (C ≤ 1000 mg/kg bw) and at the guidance value, dermal for a Category 2 classification (2000 mg/kg bw ≥ C > 1000 mg/kg bw). No classification required.

Specific target organ toxicity: single exposure (Inhalation):

No information was available.