Registration Dossier

Administrative data

Description of key information

oral LD50 > 2000 mg/kg bw

inhalation LC50(1 h) > 20 mg/m³ (read-across from 2,4,7,9-Tetramethyl-5-decyne-4,7-diol)

dermal LD50 > 2000 mg/kg bw (read-across from 2,4,7,9-Tetramethyl-5-decyne-4,7-diol)

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:
25. September 2001 - 15. October 2001
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:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
2000 mg/kg single dose at 0 h
No. of animals per sex per dose:
3 male and
3 female
Control animals:
no
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.

All animals survived the 2000 mg/kg oral dose.

Bodyweight changes were normal.

Instances of dyspnea, anogenital area wet, chromorhinorrhea and localized alopecia were noted during the observation period.

Necropsy results were normal.

Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 of 2,4,7,9-tetramethyldecane-4,7-diol is >/=2000 mg/kg bw.
Executive summary:

The oral LD50 value of 2,4,7,9-tetramethyldecane-4,7-diol in rats is greater than 2000 mg/kg body weight.

Three healthy male and three healthy female Wistar albino rats were dosed orally with
2,4,7,9-tetramethyldecane-4,7-diol at 2000 mg/kg. The rats were observed 1, 2, 3, and 4 hours post-dose and once daily for 14 days for mortality, toxicity and pharmacological effects. Body weights were recorded immediately pretest, weekly, at death and at termination in the survivors. All animals were examined for gross pathology. The test article was assigned to be a toxic class based on the mortality response noted.

All animals survived the 2000 mg/kg oral dose.

Body weight changes were normal.

Instances of dyspnea, anogenital area wet, red nasal discharge, and localized alopecia were noted during the observation period.

Necropsy results were normal.


Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Study was conducted according to EC Directive 92/69/EEC and Regulation EC/440/2008 guideline methods under GLP conditions.
Klimisch score = 1

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
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: both substances start with an acetylene group as core structure, however, in the target substance this acetylene group has been fully hydrogenated during the manufacturing process; geminal hydroxyl groups on the alpha carbon atoms; distal to the geminal hydroxyl groups is an isobutyl group (methyl isopropyl)
- 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

Since the central acetylene group in the source substance is sterically shielded by the neighbouring functional groups, this structural difference does not lead to major differences in reactivity and/or toxicity, which is demonstrated based on the available toxicological data.

Therefore, read-across from the existing toxicity studies on the source substance 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:
read-across source
Reason / purpose:
read-across: supporting information
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
Dose descriptor:
LC50
Effect level:
> 20 mg/L air
Based on:
act. ingr.
Exp. duration:
1 h
Remarks on result:
other:

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:

Material              Sex       Initial       Final       Change

Surfynol 104       M       176 g       288 g       + 112 g

- " -                    F       211 g       239 g       + 28 g

Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
20 mg/m³
Quality of whole database:
Test done before GLP and OECD Guidelines were established. This study contains data which are close to meet the criteria set forth in Regulation EC No. 440/2008 for filling REACH endpoints. The data is generated in a reliable laboratory using established protocols.

Acute toxicity: via dermal route

Link to relevant study records
Reference
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:
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: both substances start with an acetylene group as core structure, however, in the target substance this acetylene group has been fully hydrogenated during the manufacturing process; geminal hydroxyl groups on the alpha carbon atoms; distal to the geminal hydroxyl groups is an isobutyl group (methyl isopropyl)
- 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

Since the central acetylene group in the source substance is sterically shielded by the neighbouring functional groups, this structural difference does not lead to major differences in reactivity and/or toxicity, which is demonstrated based on the available toxicological data.

Therefore, read-across from the existing toxicity studies on the source substance 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:
read-across source
Reason / purpose:
read-across: supporting information
Qualifier:
according to
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
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
No clinical signs of ill health or behaioural changes were observed during study period.
Body weight:
Low body weight gain or body weight loss was noted in all animals over the first week of the study and improved weight gain over the second week.
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:
GHS criteria not met
Conclusions:
The dermal LD50 was established as exceeding 2000 mg/kg/ body weight.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
This study contains data which meet the criteria set forth in Regulation EC No. 440/2008 for filling REACH endpoints. The data is generated in a reliable laboratory using established protocols under GLP conditions. Klimisch score = 1.

Additional information

For the assessment of acute toxicity of the target substance 2,4,7,9-tetramethyldecane-4,7-diol an acute oral toxicity study is available. Supporting data are also available for the source substances 2,4,7,9-Tetramethyl-5-decyne-4,7-diol and 2,5,8,11-tetramethyldodec-6-yne-5,8-diol. An acute inhalation toxicity as well as an acute dermal toxicity study is available for the source substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol. Based on the similarly low toxicity after oral administration across this group of substances, the read-across for acute toxicity after inhalation and dermal administration as well as for other toxicological endpoint is supported. The detailed justification for read-across is attached to iuclid section 13.

 

Acute oral toxicity

The oral LD50 value of 2,4,7,9-tetramethyldecane-4,7-diol in rats is greater than 2000 mg/kg body weight. Three healthy male and three healthy female Wistar albino rats were dosed orally with the test item at 2000 mg/kg. The rats were observed 1, 2, 3, and 4 hours post-dose and once daily for 14 days for mortality, toxicity and pharmacological effects. Body weights were recorded immediately pretest, weekly, at death and at termination in the survivors. All animals were examined for gross pathology. The test article was assigned to be a toxic class based on the mortality response noted. All animals survived the 2000 mg/kg oral dose. Body weight changes were normal. Instances of dyspnea, anogenital area wet, red nasal discharge, and localized alopecia were noted during the observation period. Necropsy results were normal.

 

The oral administration to rats of 500 mg of the source substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol per kg of body weight resulted in no mortality. All animals survived, showed no abnormal clinical signs and gained weight.  Gross necropsy did not reveal any test material-related pathological changes. However, the substance was not tested up to the limit dose of current guidelines. Additional supporting data on the source substance 2,5,8,11-tetramethyldodec-6-yne-5,8-diol demonstrate, that this group of substances is in general of low acute toxicity. The LD50 in rats was determined to be 12.9 g/kg bw.

 

Acute inhalation toxicity

In an acute inhalation toxicity study young adult rats (strain not specified) (5/sex) were exposed by inhalation route to 2,4,7,9-Tetramethyl-5-decyne-4,7-diol for 1 hour (aerosol; whole body) at a concentrations 20 mg of mist per liter.  Animals then were observed for 14 days.

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.

The 1 h LC50 was > 20 mg/L.

 

Acute dermal toxicity

The purpose of this study was to assess the toxicity of 2,4,7,9-Tetramethyl-5-decyne-4,7-diol when administered to rats as 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 2,4,7,9-Tetramethyl-5-decyne-4,7-diol in rats of either sex was established as exceeding 2000 mg/kg bw.

 

Based on the available information, the acute toxicity of 2,4,7,9-tetramethyldecane-4,7-diol is low. There are no data gaps in acute toxicity. Even though there is no information on acute toxicity in humans, there is no reason to believe that the low acute toxicity observed in experimental animals would not be relevant for human health.

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.