2,4,7,9-tetramethyldec-5-yne-4,7-diol

Endpoint summary

Description of key information

According to the UN Globally Harmonized System of ClassificThe subject material when studied in male albino raation and Labelling of Chemicals (GHS) Part 3 Chapter 3.1 no classification required, 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar toxicological properties because
- they are manufactured from similar precursors under similar conditions
- they share structural similarities with common functional groups: the substances start with an acetylene group as core structure; geminal hydroxyl groups on the alpha carbon atoms; distal to the geminal hydroxyl groups is an isobutyl group (methyl isopropyl);The source substance 2,5,8,11-tetramethyldodec-6-yne-5,8-diol is an acetylenic geminalic diol surfactant containing a central acetylene functional group; two stereogenic centers consisting of carbons in alpha position to a carbon triple bond and short chain alkyl groups distal to both geminal hydroxyl groups. The acetylene group is a relatively poor hydrophobe, resulting from the hindering effect of the adjacent hydroxyl groups. In the target substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol shares the same chemical structure with only the alkyl side chains missing a CH2-unit each.
- they have similar physicochemical properties and thus, show a similar toxicokinetic behaviour
- they are expected to undergo similar metabolism: oxidation of the terminal methyl groups to result in alcohol, aldehyde and finally the corresponding acid

Therefore, read-across from the existing toxicity, ecotoxicity, environmental fate and physicochemical studies on the source substances is considered as an appropriate adaptation to the standard information requirements of REACH regulation.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
see “Justification for read-across” attached to IUCLID section 13

3. ANALOGUE APPROACH JUSTIFICATION
see “Justification for read-across” attached to IUCLID section 13

4. DATA MATRIX
see “Justification for read-across” attached to IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Sex:

male

Dose descriptor:

LD50

Effect level:

12 900 mg/kg bw

Based on:

test mat.

95% CL:

> 8 400 - < 20 100

Mortality:

one animal within 24 hours in the 8 g group
one animal within 24 hours and two within 48 hours in the 16 g group

Clinical signs:

other: At the dosage levels of 1.0 and 2.0 gm/kg. the animals were ruffled, dirty and slightly depressed after 24 hours. They appeared recovered and normal after 48 hours. At the dosage level of 4.0 gm/kg. the animals were depressed after 4-6 hours. Within 24 ho

Gross pathology:

In the gross pathologic examination, slight hemorrrhaging of the GI tract was evident in those animals dying during
the course of the study. Gross pathologic examination of the animals sacrificed a t the conclusion of the observation
period revealed nothing remarkable.

Dosage Level g/kg	Number of Animals Dosed	1	2	3	4	5	6	7	8	9	10	11	12	13	14	Total Dead 14 Days	Total Survived 14 Days	Average Initial Weight [g]	Average Final Weight [g]
1.0	5	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	5	235	280
2.0	5	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	5	220	250
4.0	5	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	5	240	275
8.0	5	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	4	210	235
16.0	5	1	2	0	0	0	0	0	0	0	0	0	0	0	0	3	2	220	245

Interpretation of results:

GHS criteria not met

Conclusions:

The subject material when studied in male albino rats has
an acute oral LD50 of 12.9 gm/kg. with 19/20 Confidence
limits of from 8.4 to 20.1 gm/kg.

Executive summary:

The subject material when studied in male albino rats has an acute oral LD50 of 12.9 gm/kg. with 19/20 Confidence limits of from 8.4 to 20.1 gm/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

12 900 mg/kg bw

Quality of whole database:

reliable with restriction

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 1971

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guide to Precautionary Labeling of Hazardous Chemicals, Seventh Edition - 1970, published by the Manufacturing Chemist´s Association

Principles of method if other than guideline:

5 male rats (average weight 176 grams) and 5 female rats (average weight 211 grams) were placed in a 306 liter chamber.  The Surfynol 104 was prepared as a 5% aqueous solution.  An air flow of five liters per minute was introduced into the chamber.  The test solution was aerosolized to provide a concentration of greater than 20 mg of mist per liter of chamber air over the one-hour period.  The test atmosphere was not analyzed.  The animals were observed daily for 14 days.

GLP compliance:

no

Test type:

other: Guide to Precautionary Labeling of Hazardous Chemicals, Seventh Edition - 1970, published by the Manufacturing Chemist´s Association

Species:

rat

Strain:

not specified

Sex:

male/female

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Duration of exposure:

ca. 1 h

Concentrations:

20 mg of mist per liter

No. of animals per sex per dose:

5 male and
5 female

Control animals:

no

Key result

Sex:

male/female

Remarks on result:

not determinable due to absence of adverse toxic effects

Ocular and nasal irritation as well as a reduction in spontaneous activity were noted in all animals at the end of the one-hour exposure period. These symptoms disappeared within three hours.

All rats survived the one-hour exposure and the 14 -day observation period (post exposure).

All animals maintained a normal appearance and gained weight over the observation period. No evidence of gross lesions was found in the animals autopsied. Body weight data are presented in the following summary:

Sex Initial Final Change

M 176 g 288 g + 112 g

F 211 g 239 g + 28 g

Material              Sex       Initial       Final       Change

Surfynol 104       M       176 g       288 g       + 112 g

- " -                    F       211 g       239 g       + 28 g

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

Based upon the results of this study, it was concluded that the Surfynol 104 sample submitted was not a toxic substance by inhalation according to specifications for such substances set forth by the Manufacturing Chemist´s Association, Inc.:
" ... a toxic substance falls within the following category: "a substance that has a median lethal concentration (LC50) in air of more than ..... 2 milligrams per liter but not more than 20 milligrams per liter of mist ..... when administrered by continuous inhalation for one hour or less to albino rats weighing between 200 grams and 300 grams each ... "

Executive summary:

Ocular and nasal irritation as well as a reduction in spontaneous activity were noted in all animals at the end of the one-hour exposure period. These symptoms disappeared within three hours.

All rats survived the one-hour exposure and the 14 -day observation period (post exposure).

All animals maintained a normal appearance and gained weight over the observation period. No evidence of gross lesions was found in the animals autopsied.

Material              Sex       Initial       Final       Change

Surfynol 104       M       176 g       288 g       + 112 g

- " -                    F       211 g       239 g       + 28 g

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

1 000 mg/m³ air

Quality of whole database:

Study has been done before the establishment of GLP, but is following the Guide to Precautionary Labeling of Hazardous Chemicals, Seventh Edition - 1970, published by the Manufacturing Chemist´s Association. Klimisch score 2.

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:

1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: according to EC Directive 92/69/EEC and Regulation EC/440/2008 guideline methods under GLP conditions

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Remarks:

Statement of GLP Compliance

Test type:

fixed dose procedure

Species:

rat

Strain:

Wistar

Sex:

male/female

Type of coverage:

occlusive

Vehicle:

propylene glycol

Duration of exposure:

24 hours

Doses:

Dose level: 2000 mg/kg body weight
Dose Volume: 10 ml/kg body weight

No. of animals per sex per dose:

5 males and
5 females

Control animals:

no

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no data on CL

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: No clinical signs of ill health or behaioural changes were observed during study period.

Gross pathology:

Macroscopic post mortem examination of the animals at termination did not reveal any significant abnormalities. Pelvic dilatation of the right kidney was noted in one males. Renal pelvic dilation is a common finding in animals of this age and strain and therefore considered not related to treatment.

Other findings:

Treated skin abnormalities:
Scales and scabs were observed on the treated skin area among two females between day 4 and 6.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

The dermal LD50 value of Surfynol 104 in rats of either sex was established as exceeding 2000 mg/kg/ body weight.

Executive summary:

This study was entitle "Assessment of acute dermal toxicity with Surfynol 104 in the rat".

The purpose of this study was to assess the toxicity of Surfynol 104 when administered to rats asa a single dermal dose.

The study was carried out in accordance with OECD Guidline No. 402, "Acute Dermal Toxicity" and EEC Directive 92/96 /EEC, Part B.3, "Acute Toxicity - Dermal". Surfynol 104 was adminestered by dermal application, to five rats of each sex, at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed at the end of the experimental period.

No mortality and no clinical signs of ill health were observed during the study. Skin abnormalities on the treated area included scales and scabs in two females between days 4 and 6. Low body weight gain or body weight loss was noted in all animals over the first week of the study and improved body weight gain over the second week. Macroscopic post mortem examination of the animals at termination did not reveal any significant abnormalities.

The dermal LD50 value of Surfynol 104 in rats of either sex was established as exceeding 2000 mg/kg/ body weight.

Based on these results and according to the EEC criteria for classification and labeling requirements for dangerous substances and preparations (EEC Directive 91/325/EEC, Amendment to Annex VI of the EEC Directive 67/548/EEC). Surfynol 104 cannot be classified and has no obligatory labeling reqiurement.

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 GLP compliant and is of high quality, Klimisch score = 1

Justification for classification or non-classification

According to the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Part 3 Chapter 3.1 no classification required, since this substance doese not cause concern of acute toxicity.