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Administrative data

Description of key information

Acute Oral (OECD 423): LD50 >2000 mg/kg.
Acute Dermal Study (OECD 402): LD50 >2000 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:
2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Compliant with current guidelines and GLP compliant
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Crj: CD(SD)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Kingston, NY
- Age at study initiation: The female rats were approximately 66 days of age at arrival at the Testing Facility.
- Weight at study initiation: The body weight range was 202 g to 226 g on the day after arrival at the Testing Facility.
- Fasting period before study: Rats were fasted overnight prior to dose administration through 3 to 4 hours postdose administration.
- Housing: The rats were individually housed in stainless steel, wire-bottomed cages.
- Diet (e.g. ad libitum): Ad libitum (except prior to dose administration)
- Water (e.g. ad libitum) Ad libitum:
- Acclimation period: The rats were acclimated for 5 days prior to assignment to study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Room temperature was targeted at 66°F to 77°F (19°C to 25°C).
- Humidity (%): The relative humidity was targeted at 30% to 70%.
- Air changes (per hr): The study rooms were maintained under conditions of positive airflow relative to a hallway and independently supplied with a minimum of 10 changes per hour of 100% fresh air that had been passed through 99.97% HEPA filters.
- Photoperiod (hrs dark / hrs light): An automatically controlled 12-hours light: 12-hours dark fluorescent light cycle was maintained.

IN-LIFE DATES: From: To: Dosing was initiated on 29 Aug 2011 and the in-life phase of the study was completed on 26 Sep 2011
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 60 and 400 mg/mL
- Amount of vehicle (if gavage): 5 mL/kg
- Justification for choice of vehicle: This is a common vehicle for this type of substance.
- Lot/batch no. (if required): M-631
- Purity: 100%

DOSAGE PREPARATION (if unusual): A standard procedure was used to prepare the test material.

CLASS METHOD (if applicable) Annex 2c
- Rationale for the selection of the starting dose: It was presumed that test material of this type would not be extremely toxic.
Doses:
The doses used on study were 300 and 2000 mg/kg.
No. of animals per sex per dose:
Six female rats were used at the 300 mg/kg dose level and six female rats were used at the 2000 mg/kg dose level.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The female rats were observed and a body weight was recorded on a daily basis.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, food consumption and necropsy observations
Statistics:
Averages and percentages were calculated for this study.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All female rats assigned to study survived until scheduled euthanasia.
Clinical signs:
Clinical observations observed considered test substance-related included: hunched posture was observed in one rat at 300 mg/kg; decreased motor activity, bradypnea, slight excess salivation, ptosis, ataxia and lacrimation were observed at 300 and 2000 mg/kg; and impaired righting reflex, low carriage and coldness to the touch were observed at 300 mg/kg. The adverse clinical observations were first observed at approximately 30 minutes postdose. These clinical observations persisted for approximately two hours in the 300 mg/kg dose groups and until the end of day post-checks in the 2000 mg/kg dose groups. All rats appeared normal on DS 2 and continued to be normal for the remainder of the study except one rat at 2000 mg/kg that was observed with mild dehydration on DS 4.
Body weight:
Body weight gains were reduced in the 2000 mg/kg dose groups, as compared with values for the rats in the 300 mg/kg dose groups on DSs 1 to 2. A body weight loss was observed in the 2000 mg/kg dose groups on DSs 2 to 3. A comparable rebound in body weight gain was observed in both 2000 mg/kg dose groups on DSs 4 to 5. The mean value for the body weight change for rats in the 2000 mg/kg dose groups (averages of Groups 1 and 2) were reduced by 25% for the first week after dose administration (calculated as DSs 1 to 8), as compared with the mean value for the rats in the 300 mg/kg dose groups (average of Groups 3 and 4). Body weight gains were comparable between the 300 and 2000 mg/kg dose groups during the second week of the study (calculated as DSs 8 to 14).
Gross pathology:
No gross lesions were identified at necropsy.

Absolute (g/day) and relative (mg/kg/day) food consumption values were reduced in the 2000 mg/kg dose groups, as compared with values for the rats in the 300 mg/kg dose groups on DSs 1 to 2, 2 to 3 and 3 to 4. A comparable rebound in absolute food consumption values was observed in both 2000 mg/kg dose groups on DSs 4 to 5 and the absolute and relative food consumption values remained generally comparable for the remainder of the study including the entire study period (calculated as DSs 1 to 14). The mean absolute food consumption value for the rats in the 2000 mg/kg dose groups (averages of Groups 1 and 2) were reduced by 12% for the first week after dose administration (calculated as DSs 1 to 8), as compared with the mean value for the rats in the 300 mg/kg dose groups (average of Groups 3 and 4). 

The mean relative food consumption value for the rats in the 2000 mg/kg dose groups (averages of Groups 1 and 2) were reduced by 19% for the first week after dose administration (calculated as DSs 1 to 8), as compared with the mean value for the rats in the 300 mg/kg dose groups (average of Groups 3 and 4). Absolute and relative food consumption values were generally comparable between the 300 and 2000 mg/kg dose groups during the second week of the study (calculated as DSs 8 to 14).  

Interpretation of results:
not classified
Remarks:
Migrated information No mortality was caused at 2000 mg/kg; however, there were adverse clinical signs, body weight loss and decreased food consumption at this dose. Criteria used for interpretation of results: EU
Conclusions:
CONCLUSION

In conclusion, administration of a single dose of 300 or 2000 mg/kg of test substance did not cause mortality. Doses of 300 and 2000 mg/kg produced adverse clinical signs that were apparent at the 30 minute postdose observation but were no longer apparent by the end of the day postdose observation. The 2000 mg/kg dose reduced body weight and food consumption the first several days after dose administration.
Executive summary:

Executive Summary

    

The objectives of this study were to determine the acute toxicity resulting from exposure to EC 202-228-8 (test substance) in Crl:CD(SD) rats, and to estimate the defined exposure ranges where lethality is expected, since death of a proportion of the animals was a major endpoint of this study.

The study design was as follows:

Text Table1
Experimental Design

Exposure Group No.

No. of Female Rats

Test Material

Dose Level

(mg/kg)a,b

Concentration

(mg/mL)

Dose Volume

(mL/kg)

1

3

Test Substance

300

60

5

2

3

Test Substance

300

60

5

3

3

Test Substance

2000

400

5

4

3

Test Substance

2000

400

5

a  Subsequent dose levels were established by the Study Director based on the results of the initial 300 mg/kg dose.

b  Rats were fasted overnight prior to dose administration through 3 to 4 hours after dose administration.

Female rats were administered the test substance once by oral gavage. The rats were fasted overnight prior to dose administration through 3 to 4 hours postdose administration. Doses were adjusted for fasted body weights taken before administration. The first day of dose administration was designated as Day 1 of study (DS 1) for each rat.

The 300 mg/kg dose level was administered to 3 female rats. No mortality and body weight gain were observed; therefore, an additional 3 female rats were dosed once with 300 mg/kg of test substance. No mortality and body weight gain were observed following dose administration; therefore, an additional 3 female rats were dosed once with 2000 mg/kg of test substance. No mortality was observed following dose administration; therefore, an additional 3 female rats were dosed once with 2000 mg/kg of test substance. All doses were based on a 5 mL/kg dose volume.  

The following parameters and end points were evaluated in this study: clinical signs, body weights, body weight changes, food consumption, and gross necropsy findings.

Clinical observations observed considered test substance-related included hunched posture, decreased motor activity, bradypnea, slight excess salivation, ptosis, ataxia, lacrimation, impaired righting reflex, low carriage and coldness to the touch. The adverse clinical observations were first observed at approximately 30 minutes postdose. These clinical observations persisted for approximately two hours in the 300 mg/kg dose groups and until the end of day post-checks in the 2000 mg/kg dose groups. All rats appeared normal on DS 2 and continued to be normal for the remainder of the study. 

Body weight gains were reduced in the 2000 mg/kg dose groups, as compared with values for the rats in the 300 mg/kg dose groups on DSs 1 to 2. A body weight loss was observed in the 2000 mg/kg dose groups on DSs 2 to 3. A comparable rebound in body weight gain was observed in both 2000 mg/kg dose groups on DSs 4 to 5. 

Absolute and relative food consumption values were reduced in the 2000 mg/kg dose groups, as compared with values for the rats in the 300 mg/kg dose groups on DSs 1 to 2, 2 to 3 and 3 to 4. A comparable rebound in absolute food consumption values was observed in both 2000 mg/kg dose groups on DSs 4 to 5 and the absolute and relative food consumption values remained generally comparable for the remainder of the study.  

No gross lesions were identified at necropsy.

In conclusion, administration of a single dose of 300 or 2000 mg/kg of test substance did not cause mortality. Doses of 300 and 2000 mg/kg produced adverse clinical signs that were apparent at the 30 minute postdose observation, but were no longer apparent by the end of the day postdose observation. The 2000 mg/kg dose reduced body weight and food consumption the first several days after dose administration. 

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Modern GLP study conducted in accordance with OECD test guidelines. Klimisch score 1

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:
31 January to 21 February 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Compliant with current guidelines and GLP compliant
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River UK, Margate
- Age at study initiation: Approximately 8 to 10 weeks old
- Weight at study initiation: 198 and 230 g (males) and 213 and 232 g (females)
- Fasting period before study: No
- Housing: Singly housed
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Approximately 22°C on each day
- Humidity (%): approximately 32% to 49%.
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 h light/dark cycle

IN-LIFE DATES: From: To: 31 January to 21 February 2012
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: ~38 cm2 (males) and ~25 cm2 (females)
- % coverage: ~12% (males), ~8% (females)
- Type of wrap if used: Micropore and Sleek tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Sterile water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 426 mg (males), 444 mg (females)
- Concentration (if solution): NA
- For solids, paste formed: no
Duration of exposure:
24 h
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 5 times on the day of dosing and once daily from Day 2 until Day 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weights
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths among animals treated with 2 (2 naphthoxy)ethanol at 2000 mg/kg.
Clinical signs:
There were no signs of systemic toxicity in any animal at any observation timepoint.
Clinical signs were restricted to staining to test site, which was seen in 2 males on Day 2, and test item residues at the test site, which was seen in 4 females on Day 2. No other clinical signs were recorded.
Body weight:
Body weight gain was considered to be acceptable for rats of this age and strain.
Gross pathology:
There were no abnormal findings noted at necropsy.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study, the median lethal dermal dosage (LD50) for 2 (2 naphthoxy)ethanol in Sprague-Dawley rats was estimated to be greater than 2000 mg/kg.
This study is considered to be relevant, reliable and adequate for risk assessment and for classification purposes.
Executive summary:

The objective of this study was to assess the adverse effects which can follow within a short period of time after a single dermal administration of 2‑(2‑naphthoxy)ethanol to rats.

The test item was administered to a single group of 5 male and 5 female Sprague-Dawley rats. The study design was as follows:

Text Table1
Experimental Design

Dose Level
(mg/kg)

Animal Numbers

Males

Females

2000

1 to 5

6 to 10

 

The test item was administered, as supplied, onto the moistened dorsal trunk under a gauze patch, also moistened, which was covered with semi‑occlusive tape, then secured with occlusive tape (ie the site was fully occluded). The dressings remained in place for 24 h. The dose was calculated on the basis of the body weights of the animals on the day of dosing. Animals were observed for signs of reaction to treatment 5 times on the day of dosing and once daily from Day 2 until the end of the observation period on Day 15. Body weights were recorded weekly and all animals were subjected to a necropsy examination.

The following parameters and end points were evaluated in this study: clinical signs, body weights, body weight changes, and gross necropsy findings.

There were no unscheduled deaths during the observation period.

There were no systemic signs of toxicity noted in any animal at any observation timepoint and local findings at the dosing site were restricted to staining or test item residues at the test site, which were seen in 6 animals on Day 2 only.

Body weight gain was considered to be acceptable for rats of this age and strain. No abnormal findings were noted at necropsy.

Under the conditions of the study, the median lethal dermal dosage (LD50) for 2-(2-naphthoxy)ethanol in Sprague-Dawley rats was estimated to be greater than 2000 mg/kg.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Acute toxicity oral

Testing conducted in accordance with OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method) reported that no deaths occurred up to an oral dose of EC 202-228-8 at 2000 mg/kg. Doses of 300 and 2000 mg/kg produced adverse clinical signs that were apparent at the 30 minute postdose observation, but were no longer apparent by the end of the day. The 2000 mg/kg dose reduced body weight and food consumption the first several days after dose administration. The median lethal oral dose (LD50) for EC 202-228-8 in Sprague-Dawley rats is therefore greater than 2000 mg/kg.

Acute Dermal Study

Testing conducted in accordance with OECD guideline 402 reported no unscheduled deaths during the observation period. There were no systemic signs of toxicity noted in any animal at any observation timepoint and local findings at the dosing site were restricted to staining or test item residues at the test site, which were seen in 6 animals on Day 2 only. Body weight gain was considered to be acceptable for rats of this age and strain. No abnormal findings were noted at necropsy. Under the conditions of the study, the median lethal dermal dosage (LD50) for EC 202-228-8 in Sprague-Dawley rats was therefore greater than 2000 mg/kg.

Acute Inhalation Study

In accordance with Section 8.5 of Annex VIII of the REACH Regulation, a study of the acute inhalation toxicity is not required, since there is very low potential for inhalation exposure to the substance. Studies of acute toxicity of the registration substance via oral exposure and via dermal exposure have been provided (see sections 7.2.1 and 7.2.3 of the IUCLID dossier).


Justification for selection of acute toxicity – oral endpoint
Modern GLP study conducted in accordance with OECD test guidelines. Klimisch score 1

Justification for selection of acute toxicity – dermal endpoint
Modern GLP study conducted in accordance with OECD test guidelines. Klimisch score 1

Justification for classification or non-classification

Acute toxicity oral

Results from a study conducted in accordance with OECD 423 guideline did not produce test-material-related mortality. The acute median lethal oral dose (LD50) was found to exceed 2000 mg/kg, therefore the test material was considered to have no significant acute toxic risk if swallowed and did not meet the criteria for classification according to CLP Regulation (EC) No 1272/2008.

Acute Dermal Toxicity

Results from a study conducted in accordance with OECD 402 guideline did not produce test-material-related mortality.The acute median lethal oral dose (LD50) was found to exceed 2000 mg/kg, therefore the test material was considered to have no significant acute toxic risk if in contact with the skin and did not meet the criteria for classification according to CLP Regulation (EC) No 1272/2008.