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Administrative data

Description of key information

Acute Oral Toxicity:

The test material was determined to have an acute oral toxicity LD50 of >15000 mg/kg bw (in rats). No deaths were observed.

Acute Dermal Toxicity:

The acute dermal toxicity of the substance (EC 406-176-9) has been assessed by a OECD 402 study on substance itself and supported by reading across the results of studies conducted on two structurally similar analgoue substances. It is proposed that these results can be used in the assessment of the target substance (EC 406-176-9).

OECD 402 study on target substance (EC 406-176-9):

The acute dermal median lethal dose (LD50) of the test material in guinea pigs was found to be > 2000 mg/kg bodyweight. In 5 female and 5 male animals tested at 2000 mg/kg bodyweight there was no mortality observed and no clinical signs of systemic toxicity.

Source Substance; 1,3:2,4-bis-O-(3,4-dimethylbenzylidene)-D-glucitol (EC-413 -110 -2):

A study was performed to assess the acute dermal toxicity of the test material (EC 413-110-2) in the Sprague-Dawley CD strain rat.

A group of 10 animals (5 males and 5 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 14 days after the day of treatment and were then killed for gross pathological examination.

There were no deaths. No signs of systemic toxicity or 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 > 2000 mg/kg bodyweight.

Source Substance; 1-(2,6-bis(4-tolyl)-1,3-dioxano(5,4-d)-1,3-dioxan-4-yl)ethane-1,2-diol (EC 402-950-5):

The purpose of the study is to determine the acute dermal toxicity of technical GEL-ALL-MD (EC 402-950-5) to the rat.

Groups of 5 male and 5 female Sprague-Dawley rats received a single, 24 hour occluded, topical application of 2100 mg Technical Gel-ALL-MD/kg bodyweight, moistened with 0.5% w/v sodium carboxymethylcellulose in distilled water. A further 5 male and 5 female control animals were treated similarly except that no test material was applied to the skin. Animals were observed for 14 days after treatment and then examined post mortem.

There were no mortalities, no treatment-related clinical signs and no evidence of skin irritation. No treatment-related effects on bodyweight were recorded and no abnormalities were seen post-mortem.

In both sexes the acute dermal LD50 was greater than 2100 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:
experimental study
Adequacy of study:
key study
Study period:
1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Principles of method if other than guideline:
Acute oral toxicity study. Limit test at dose level 15000 mg/kg bw in rats
GLP compliance:
not specified
Test type:
fixed dose procedure
Limit test:
yes
Specific details on test material used for the study:
Not available
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Doses:
15000 mg/kg
No. of animals per sex per dose:
10 per sex at 15000 mg/kg bw
Control animals:
no
Details on study design:
- Duration of observation period following administration: Hourly for the first 6 hrs after intake of the test substance. Daily for 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 15 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths.
Clinical signs:
15-120 minutes after exposure, spontaneous activity decreased slightly.
Body weight:
After 1 day, food intake was comparably lower. Body weight was not influenced.
Gross pathology:
Necropsy did not show abnormal findings.
Interpretation of results:
GHS criteria not met
Conclusions:
The test material was determined to have an acute oral toxicity LD50 of >15000 mg/kg bw (in rats)
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
15 000 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

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
not specified
Test type:
fixed dose procedure
Limit test:
yes
Species:
guinea pig
Strain:
other: Bor: DHPW (SPF)
Sex:
male/female
Type of coverage:
occlusive
Vehicle:
olive oil
Duration of exposure:
6 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 females and 5 males at 2000 mg/kg (plus 2 additional reserve animals for each sex).
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths.
Clinical signs:
No abnormal findings for systemic toxicity.
No abnormal finding for local irritation.
Gross pathology:
No abnormal findings in organs observed.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal median lethal dose (LD50) of the test material in guinea pigs was found to be > 2000 mg/kg bodyweight. In 5 female and 5 male animals tested at 2000 mg/kg bodyweight there was no mortality observed and no clinical signs of systemic toxicity.
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
02 October 1997 to 16 October 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: males: 215 to 243 g; females: 208 to 230 g
- Housing: animals were housed in suspended polypropylene cages furnished with wood flakes. The animals were housed individually during the 24-h exposure period and in groups of 5, by sex, for the remainder of the study.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 22 °C
- Humidity (%): 50 to 74 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/ 12
- On one occasion the relative humidity was above the limit specified in the protocol (70 %). This deviation was not considered to affect the purpose or integrity of the study.
Type of coverage:
semiocclusive
Vehicle:
other: moistened with arachis oil BP.
Details on dermal exposure:
TEST SITE
- % coverage: 10 % of the total body surface
- Type of wrap if used: 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 Blenderm wrapped around each end.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated skin and surrounding hair was wiped with cotton wool moistened with arachis oil BP to remoe any residual test material.
- Time after start of exposure: 24 h

TEST MATERIAL
- The test material, as received, was applied uniformly to an area of shorn skin which had been previously moistened with arachis oil BP.
Duration of exposure:
24 h
Doses:
2000 mg/kg
No. of animals per sex per dose:
5/ sex/ dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 h after dosing and subsequently once daily for 14 aysd. Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: dermal reactions (scored according to the Draize scale).
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted during the study.
Body weight:
All animals showed an expected gain in bodyweight during the study.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
Dermal reactions: No signs of skin irritation were noted.
Interpretation of results:
GHS criteria not met
Conclusions:
The dermal toxicity of the test material was assessed according to OECD guideline 402. The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be > 2000 mg/kg bodyweight.
Executive summary:

A study was performed to assess the actue 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" and Method B3 of Commission Directive 92/69/EEC.

A group of 10 animals (5 males and 5 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 14 days after the day of treatment and were then killed for gross pathological examination.

There were no deaths. No signs of systemic toxicity or 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 > 2000 mg/kg bodyweight.

Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
It is proposed that the structural similarity and properties of the target substance and the structural analogue (sources substance) are sufficiently close for there to be a reasonable expectation of similar effects.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source chemical:
1,3:2,4-bis-O-(3,4-dimethylbenzylidene)-D-glucitol (EC 413-110-2, CAS 135861-56-2)

Target chemical:
2,6-bis(4-ethylphenyl)perhydro-1,3,5,7-tetraoxanaphth-4-ylethane-1,2-diol (EC 406-176-9, CAS 79072-96-1)

3. ANALOGUE APPROACH JUSTIFICATION
Based on the structural similarity of the source substances and target substance, similarity of physic-chemical properties and similarity in experimental (eco)toxicological test data it is concluded that target substance and the structural analogue (source substance) are sufficiently close for there to be a reasonable expectation of similar effects, for the endpoints where results have been read-across.

4. DATA MATRIX
Please see 'Read-across justification to support the REACH registration of EC 406-176-9' document attached in section 13.
Reason / purpose:
read-across source
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted during the study.
Body weight:
All animals showed an expected gain in bodyweight during the study.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
Dermal reactions: No signs of skin irritation were noted.
Interpretation of results:
GHS criteria not met
Conclusions:
The dermal toxicity of the test material was assessed according to OECD guideline 402. The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be > 2000 mg/kg bodyweight.
Executive summary:

A study was performed to assess the actue dermal toxicity of the test material (structural analogue source substance EC 413-110-2) 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" and Method B3 of Commission Directive 92/69/EEC.

A group of 10 animals (5 males and 5 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 14 days after the day of treatment and were then killed for gross pathological examination.

There were no deaths. No signs of systemic toxicity or 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 > 2000 mg/kg bodyweight.

It is proposed that this result can be used in the assessment of the target substance (EC 406-176-9).

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Study conducted between April 1988 and June 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of relevant results.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
other: modified procedure described by Noakes and Sanderson (similar to standard acute method)
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River UK, Ltd, Manston Road, Margate, Kent
- Age at study initiation: Males were between 48 to 50 days old and females were between 56 to 65 days old
- Weight at study initiation: 278 g to 342 g for Males and 211 g to 267 g for Females
- Fasting period before study: not stated in report
- Housing: Rats were housed in pairs by sex and in steel mesh cages
- Diet (e.g. ad libitum): Free acess to Modified Expanded S.Q.C Rat and Mouse Diet No. 1
- Water (e.g. ad libitum): tap water
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):18 to 22 deg C
- Humidity (%): 44 to 54%
- Air changes (per hr): not stated in report
- Photoperiod (hrs dark / hrs light): 12 hours light followed by 12 hours of darkness

IN-LIFE DATES: From: Day of dosing (day 1) To: Day of sacrifice (day 14)
Type of coverage:
occlusive
Vehicle:
other: moistened with 0.5% sodium carboxymethyl in distilled water.
Details on dermal exposure:
TEST SITE
- Area of exposure: 6 cm by 10 cm
- Type of wrap if used: aluminium foil (held in place by an encircling band of waterproof plaster).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): treated skin was washed with soap and water to remove residual test material and then rinsed with water and dried.
- Time after start of exposure: 24 hours

TEST MATERIAL
- For solids, paste formed: yes, test material was moistened with 0.5% w/v solution sodium carboxymethylcellulose in distilled water and applied to the shaved area at a dose level of 2100 mg/kg.



Duration of exposure:
24 hours
Doses:
0 (control) and 2100 mg/kg
No. of animals per sex per dose:
5 males and 5 females were tested at both the 0 and 2100 mg/kg dose range (e.g. 20 animals in total)
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Animals were observed for clinical signs and behaviour frequently on the day of treatment, at least once each morning and afternoon on working days thereafter and at leaast once each other day. Bodyweights were recorded immediately prior to treatment on Day 1, on Day 8 and immediately prior to termination on Day 15.

- Necropsy of survivors performed: yes - all animals were killed by CO2 asphyxiation on Day 15 and subjected to gross post-mortem examination for external abnormalities and for abnormalities of the thoracic and abdominal viscera.
- Other examinations performed: skin irritation - after removal of the plaster, skin treatment sites were examined daily for evidence of skin irritation.
Statistics:
The significance of difference between bodyweight change of control and test groups was estimated by the two sample test of Dunnett.
Preliminary study:
Range finding with 1 male and 1 female: no evidence of toxicity or skin irritation
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 100 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths during the study.
Clinical signs:
There were no treatment related clinical signs during the study.
Body weight:
Bodyweight and bodyweight change of animals treated with test material were similar to those of the controls.
Gross pathology:
There were no abnormal findings
Other findings:
Skin irritation: There was no evidence of skin irritation.
Interpretation of results:
other: not classified under EU CLP
Conclusions:
In both sexes, the acute dermal LD50 was greater than 2100 mg/kg bw.
Executive summary:

The purpose of the study is to determine the acute dermal toxicity of techncial GEL-ALL-MD to the rat.

Groups of 5 male and 5 female Sprague-Dawley rats received a single, 24 hour occluded, topical application of 2100 mg Technical Gel-ALL-MD/kg bodyweight, moistened with 0.5% w/v sodium carboxymethylcellulose in distilled water. A further 5 male and 5 female control animals were treated similarly except that no test material was applied to the skin. Animals were observed for 14 days after treatment and then examined post mortem.

There were no mortalities, no treatment-related clinical signs and no evidence of skin irritation. No treatment-related effects on bodyweight were recorded and no abnormalities were seen post-mortem.

In both sexes the acute dermal LD50 was greater than 2100 mg/kg bw.

Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
It is proposed that the structural similarity and properties of the target substance and the structural analogue (sources substance) are sufficiently close for there to be a reasonable expectation of similar effects.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source chemical:
1-(2,6-bis(4-tolyl)-1,3-dioxano(5,4-d)-1,3-dioxan-4-yl)ethane-1,2-diol (EC 402-950-5, CAS 87826-41-3)

Target chemical:
2,6-bis(4-ethylphenyl)perhydro-1,3,5,7-tetraoxanaphth-4-ylethane-1,2-diol (EC 406-176-9, CAS 79072-96-1)

3. ANALOGUE APPROACH JUSTIFICATION
Based on the structural similarity of the source substances and target substance, similarity of physic-chemical properties and similarity in experimental (eco)toxicological test data it is concluded that target substance and the structural analogue (source substance) are sufficiently close for there to be a reasonable expectation of similar effects, for the endpoints where results have been read-across.

4. DATA MATRIX
Please see 'Read-across justification to support the REACH registration of EC 406-176-9' document attached in section 13.
Reason / purpose:
read-across source
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 100 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths during the study.
Clinical signs:
There were no treatment related clinical signs during the study.
Body weight:
Bodyweight and bodyweight change of animals treated with test material were similar to those of the controls.
Gross pathology:
There were no abnormal findings
Other findings:
Skin irritation: There was no evidence of skin irritation.
Interpretation of results:
other: not classified under EU CLP
Conclusions:
In both sexes, the acute dermal LD50 was greater than 2100 mg/kg bw.
Executive summary:

The purpose of the study is to determine the acute dermal toxicity of techncial GEL-ALL-MD (structural analogue source substance EC 402-950-5) to the rat.

Groups of 5 male and 5 female Sprague-Dawley rats received a single, 24 hour occluded, topical application of 2100 mg Technical Gel-ALL-MD/kg bodyweight, moistened with 0.5% w/v sodium carboxymethylcellulose in distilled water. A further 5 male and 5 female control animals were treated similarly except that no test material was applied to the skin. Animals were observed for 14 days after treatment and then examined post mortem.

There were no mortalities, no treatment-related clinical signs and no evidence of skin irritation. No treatment-related effects on bodyweight were recorded and no abnormalities were seen post-mortem.

In both sexes the acute dermal LD50 was greater than 2100 mg/kg bw.

It is proposed that this result can be used in the assessment of the target substance (EC 406-176-9)

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Justification for classification or non-classification

Acute toxicity: via oral route:The test material did not meet the criteria for classification as acutely toxic via the oral route according to Regulation 1272/2008 (CLP) as the LD50of >2000 mg/kg is above the threshold for classification.

Acute toxicity: via dermal route:The test material did not meet the criteria for classification as acutely toxic via the dermal route according to Regulation 1272/2008 (CLP) as the LD50of >2000 mg/kg is above the threshold for classification.