Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Acute oral LD50 > 2000 mg/kg bw.

Acute dermal LD50 > 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
14 January 1997 to 06 March 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with OECD & EU test guidelines in compliance with GLP and reported with a valid GLP certificate.
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Male and female Sprague-Dawley CD (Crl:CD BR) strain rats supplied by Charles River (UK) Ltd., Margate, Kent, UK. were used. At the start of the main study the males weighed 230 to 251g, and the females 203 to 2298, and were eight to twelve weeks of age. After an acclimatisation period of at least five days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card.
The animals were housed in groups of up to five by sex in solid-floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food (Rat and Mouse Expanded Diet No. 1, Special Diets Services Limited, Witham, Essex, UK) was allowed throughout the study.
The animal room was maintained at a temperature of 20 to 21 °C and relative humidity of 46 to 55%. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.
Doses:
2000 mg/kg
No. of animals per sex per dose:
Range finding study: 1 male & 1 female
Main study: 5 males & 5 females
Control animals:
no
Details on study design:
Range-finding Study: A range-finding study was performed to establish a dosing regime as follows: IN TABLE FORM ATTACHED UNDER Any other information.

The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for five days.
Individual bodyweights were recorded on the day of dosing to allow calculation of individual treatment volumes. No necropsies were performed

Main Study: Based on the results of the range-finding study a further group of animals was treated as follows: IN TABLE FORM - ATTACHED UNDER Any other information.
The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
Individual bodyweights were recorded prior to dosing on Day 0 and on Days 7 and 14.
At the end of the study the animals were killed by cervical dislocation and subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Statistics:
Data evaluations included the relationship, if any, between the animals' exposure to the test material and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects.
Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made.
Preliminary study:
Range-finding Study: There were no deaths or clinical signs of toxicity.
Based on this information, a dose level of 2000 mg/l
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
other: No signs of systemic toxicity were noted during the study.
Gross pathology:
No abnormalities were noted at necropsy.

TABLE 2: INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN THE MAIN STUDY

Dose Level mg/kg

Animal Number and Sex

Effects Noted After Dosing (Hours)

Effects Noted During Period After Dosing (Days)

½

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

3-0 Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-1 Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-2 Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-3 Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-4 Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

4-0 Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

4-1 Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

4-2 Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

4-3 Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

4-4 Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0 = no signs of systemic toxicity

 

TABLE 3: INDIVIDUAL BODYWEIGHTS AND WEEKLY BODYWEIGHT CHANGES IN THE MAIN STUDY

Dose Level mg/kg

Animal Number and Sex

Bodyweight (g) at Day

Bodyweight Gain (g) During Week

0

7

14

1

2

2000

3-0 Male

230

301

348

71

47

3-1 Male

251

300

3378

49

37

3-2 Male

239

304

351

65

47

3-3 Male

232

308

374

76

66

3-4 Male

233

306

362

73

56

4-0 Female

219

242

269

23

27

4-1 Female

211

240

266

29

26

4-2 Female

205

228

242

23

14

4-3 Female

203

232

250

29

18

4-4 Female

229

250

269

21

19

 

TABLE 4: INDIVIDUAL NECROPSY FINDINGS IN THE MAIN STUDY

Dose Level mg/kg

Animal Number and Sex

Time of Death

Macroscopic Observations

2000

3-0 Male

Killed Day 14

No abnormalities detected

3-1 Male

Killed Day 14

No abnormalities detected

3-2 Male

Killed Day 14

No abnormalities detected

3-3 Male

Killed Day 14

No abnormalities detected

3-4 Male

Killed Day 14

No abnormalities detected

4-0 Female

Killed Day 14

No abnormalities detected

4-1 Female

Killed Day 14

No abnormalities detected

4-2 Female

Killed Day 14

No abnormalities detected

4-3 Female

Killed Day 14

No abnormalities detected

4-4 Female

Killed Day 14

No abnormalities detected

 

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test material, NAUGALUBE 531, in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. No symbol and risk phrase are required according to EU labelling regulations.
Executive summary:

Astudy was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley CD strain rat. The method followed that in the OECD Guidelines for Testing of Chemicals No. 401 "Acute Oral Toxicity" (adopted 24 February 1987) and Method B1 of Commission Directive 92/69/EEC (which constitutes Annex V of CouncilDirective 67/548/EEC). The study was performed in compliance with the Principles of Good Laboratory Practice (GLP) and reported with a valid GLP certificate.

 

The results may be used as a basis for classification and labelling under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 93/21/EEC) relating to the classification, packaging and labelling of dangerous substances.

 

Following a range-finding study, a group of ten fasted animals (five males and five females) was given a single oral dose of undiluted test material at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of dosing and were then killed and subjected to gross pathological examination.

 

There were no deaths. No signs of systemic toxicity were noted during the study.

 

All animals showed an expected gain in bodyweight during the study.

 

No abnormalities were noted at necropsy.

 

The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. No symbol and risk phrase are required according to EU labelling regulations.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
11 to 25 March 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with OECD & EU test guidelines in compliance with GLP and reported with a valid GLP certificate.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Five male and five female Sprague-Dawley CD (Crl : CD BR) strain rats supplied by Charles River (UK) Ltd, Margate, Kent were used. At the start of the study the males weighed 208 to 229g, and the females 21 6 to 239g, and were approximately eight to twelve weeks old. After a minimum acclimatisation period of five days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card.
The animals were housed in suspended polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study. Free access to mains drinking water and food (Rat and Mouse Expanded Diet No.1, Special Diets Services Limited, Witham, Essex, UK) was allowed throughout the study.
The animal room was maintained at a temperature of 19 to 22 °C and relative humidity of 47 to 53%. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
On the day before treatment the back and flanks of each animal were clipped free of hair using veterinary clippers.
The calculated volume of the test material, as received, was applied uniformly to an area of shorn skin (approximating to 10% of the total body surface area) using a graduated syringe. A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage. The bandage was further secured with a piece of BLEN DERM wrapped around each end. The animals were caged individually for the 24-hour exposure period. Shortly after dosing the dressings were examined to ensure that they were securely in place.
After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material. The animals were returned to group housing for the remainder of the study period.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males and 5 females used
Control animals:
not required
Details on study design:
The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored according to the following scale from Draize J H (1 977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC
Any other skin reactions, if present were also recorded.
Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
At the end of the study the animals were killed by cervical dislocation and subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Statistics:
Data evaluations included the relationship, if any, between the animal's exposure to the test material and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects.
Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test material was made.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
other: No signs of systemic toxicity were noted during the study.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
No signs of skin irritation were noted during the study.

TABLE 1: INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA

Dose Level mg/kg

Animal Number and Sex

Effects Noted After Dosing (Hours)

Effects Noted During Period after Dosing

(Days)

½

1

2

3

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

1-0 Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-1 Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-2 Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-3 Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-4 Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-0 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-1 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-2 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-3 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-4 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0 = no signs of systemic toxicity

 

TABLE 2: INDIVIDUAL DERMAL REACTIONS

Dose Level mg/kg

Animal Number and Sex

Observation

Effects Noted After Initiation of Exposure (Days)

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

1-0 Male

Erythema

Oedema

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-1 Male

Erythema

Oedema

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-2 Male

Erythema

Oedema

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-3 Male

Erythema

Oedema

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-4 Male

Erythema

Oedema

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-0 Female

Erythema

Oedema

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-1 Female

Erythema

Oedema

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-2 Female

Erythema

Oedema

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-3 Female

Erythema

Oedema

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-4 Female

Erythema

Oedema

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0 = no signs of dermal irritation

 

TABLE 3: INDIVIDUAL BODYWEIGHTS AND WEEKLY BODYWEIGHT CHANGES

Dose Level

mg/kg

Animal Number and Sex

Bodyweight (g) at Day

Bodyweight Gain (g) During Week

0

7

14

1

2

2000

1-0 Male

229

275

328

46

53

1-1 Male

215

238

259

23

21

1-2 Male

208

254

296

46

42

1-3 Male

218

261

305

43

44

1-4 Male

222

271

319

49

48

2-0 Female

222

233

245

11

12

2-1 Female

219

231

243

12

12

2-2 Female

216

236

241

20

5

2-3 Female

239

256

271

17

15

2-4 Female

223

223

235

2

10

 

TABLE 4: INDIVIDUAL NECROPSY FINDINGS

Dose Level mg/kg

Animal Number and Sex

Time of Death

Macroscopic Observations

2000

1-0 Male

Killed Day 14

No abnormalities detected

1-1 Male

Killed Day 14

No abnormalities detected

1-2 Male

Killed Day 14

No abnormalities detected

1-3 Male

Killed Day 14

No abnormalities detected

1-4 Male

Killed Day 14

No abnormalities detected

2-0 Female

Killed Day 14

No abnormalities detected

2-1 Female

Killed Day 14

No abnormalities detected

2-2 Female

Killed Day 14

No abnormalities detected

2-3 Female

Killed Day 14

No abnormalities detected

2-4 Female

Killed Day 14

No abnormalities detected

 

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of the test material, NAUGALUBE 531, in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. No symbol and risk phrase are required according to EU labelling regulations.
Executive summary:

A study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley CD strain rat. The method used followed that described in the OECD Guidelines for Testing of Chemicals No. 402 "Acute Dermal Toxicity" (adopted 24 February 1987) and Method B3 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). The study was performed in accordance with the Principles of Good Laboratory Practice (GLP) and reported with a valid GLP certificate.

 

The results may be used as a basis for classification and labelling under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 93/21/EEC) relating to the classification, packaging and labelling of dangerous substances.

A group of ten animals (five males and five females) was given a single 24-hour, semi occluded dermal application to intact skin at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of treatment and were then killed for gross pathological examination.

 

There were no deaths. No signs of systemic toxicity were noted during the study. No signs of skin irritation were noted during the study.

 

All animals showed an expected gain in bodyweight during the study.

No abnormalities were noted at necropsy.

 

The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. No symbol and risk phrase are required according to EU labelling regulations.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

The supporting studies for the acute oral and dermal results supports the findings in the key studies - not classified.

The read across to the structural analogue has been identified as the key study as the data is better quality (Klimisch 1) compared to the supporting studies (Klimisch 4) performed on the actual substance being registered.

Justification for selection of acute toxicity – oral endpoint

Study performed to OECD & EU test guidelines. Substance is a read across to a structural analogue.

Justification for selection of acute toxicity – dermal endpoint

Study performed to OECD & EU test guidelines. Substance is a read across to a structural analogue.

Justification for classification or non-classification

Based on the data available the substance does not trigger any of the requirements for classification. The registered substance is therefore not classified.