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Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

Alchisor TAL 145 can be characterised according to three constituents: Hydrocarbons C11-C14, n-alkanes, isoalkanes, cyclics, aromatics (2-25%), dodecan-1-ol and tetradecan-1-ol. As defined in the Read-Across Justification Document in section 13, data provided for these constituents when considered together is representative of Alchisor TAL 145and suitable for assessment purposes. Study data for each constituent has been evaluated. In a protective approach the most sensitive study result from across the three constituents has been identified and used to address the hazard endpoint in question.

As detailed in Table 1below, 7 reproductive toxicity related study reports are available for constituents of Alchisor TAL 145. Adequate reliable data is represented for each constituent. Therefore using our protective approach the dataset is a reliable adequate basis for Alchisor TAL 145 assessment purposes.

 

Table 1:Toxicity to Reproduction Key/Supporting Studies for Constituents of Alchisor TAL 145

 

 

Constituents of Alchisor TAL 145

 

Reference

Hydrocarbons C11 -C14, n-alkanes, isoalkanes, cyclics, aromatics (2 -25%)

Dodecan-1-ol

Tetradecan-1-ol

Hansen 1992

 

Key

Key (read across)

Global ICCA 2005

 

 

Supporting

Scientific Associates 1966

 

Key (read across)

Key (read across)

Exxon 1980

Key

 

 

McKee 1990

Key (read across)

 

 

Sasol 1995

Key (read across)

 

 

MHW Japan 1996

Key (read across)

 

 

 

C9-C14 Aliphatics (2-25% Aromatics)

 

The Hydrocarbons C11-C14, n-alkanes, isoalkanes, cyclics, aromatics (2-25%) components of Alchisor TAL 145 were examined for reproductive toxicity in a reproduction/ developmental toxicity screening test (OECD TG 421).  Hydrocarbons C11-C14, n-alkanes, isoalkanes, cyclics, aromatics (2-25%) fluids were administered by inhalation at a dose of 0,100, and 300 ppm to groups of rats. It was concluded that Hydrocarbons C11-C14, n-alkanes, isoalkanes, cyclics, aromatics (2-25%) fluids did not induce reproductive toxicity in the offspring or in the parental animals.  Therefore, the NOAEL was determined to be >300 ppm (Exxon 1980)

 

As read across evidence, reproductive toxicity studies are available fordecane,undecane and C9 aromatics hydrocarbon fluids.Decane was screened for Reproductive /developmental toxicity in an OECD 422 equivalent screening study. Groups of 10 male or female SD rats were oral gavage dosed with 0, 25, 150 & 100mg/kg. There were no treatment related effects at any of the dose levels on any reproductive parameter measured. Consequently it was concluded that oral dosing of decane to rats produced no evidence of reproductive effects. The NOAEL for reproductive toxicity was >1000mg/kg (Sasol 1995).

 

Undecane was examined for reproductive toxicity in a reproduction / developmental toxicity screening test (OECD TG 421).  Undecane was administered by oral gavage to rats at doses of 0,100,300 and 1000mg/kg/day. It was concluded that C9-14 Aliphatics (<2% Aromatics) hydrocarbon fluids did not induce reproductive toxicity in the offspring or in the parental animals.  Therefore, the NOAEL was determined to be 1000 mg/kg/day (MHW 1996). 

 

C9 Aromatics hydrocarbon fluids were examined for reproductive toxicity in a two-generation reproductive study.  The C9 Aromatics hydrocarbon fluids represent the aromatic constituency of the C9-14 aliphatics (2-25% aromatic) hydrocarbon fluids.  C9 Aromatics hydrocarbon fluids were administered to mice by inhalation at test atmospheres of 0,100, 500 and 1500ppm. It was concluded that C9-14 Aliphatics (<2% Aromatics) hydrocarbon fluids did not induce reproductive toxicity in the offspring or in the parental animals.  Therefore, the NOAEC (inhalation) for reproductive toxicity for the P, F1, and F2 generation was >=1500 ppm (McKee 1990). Based on this study and the lack of systemic toxicity and read-across data, C9-C14 aliphatic, 2-25% aromatic hydrocarbon fluids, are not expected to be reproductive toxicants.

 

Based on these studies and the lack of systemic toxicity and read-across data, C9-C14 aliphatics (2-25% aromatics) are not expected to be reproductive toxicants.

Dodecan-1-ol

A combined repeat dose and reproductive/developmental toxicity screening study reported a lack of effects on the reproductive organs of male and female rats receiving dodecan-1-ol (NOAEL > 2000 mg/kg/bw) (Hansen 1992, rel; 2). A read across feeding study reported a lack of effects on the reproductive organs of rats receiving hexan-1-ol (NOAEL 1127 mg/kg) (Scientific Associates Inc., 1966, Klimisch 2). No adverse effects were noted at any of the dose levels administered during the study.

Tetradecan-1-ol

Read across data from a combined repeat dose and reproductive/developmental toxicity screening study reported a lack of effects on the reproductive organs of male and female rats receiving dodecan-1-ol (NOAEL > 2000 mg/kg/bw) (Hansen 1992, Klimisch 2). This study also reported a NOAEL for reproductive effects to be 2000 mg/kg/bw. The same feeding study presented for dodecan-1-ol (Scientific Assocaies Inc, 1966) was used as read across data and reported a lack of effects on the reproductive organs of rats receiving hexan-1-ol (NOAEL 1127 mg/kg) (Scientific Associates Inc., 1966, Klimisch 2). No adverse effects were noted at any of the dose levels administered during the study. It should be noted that C6, hexan-1-ol has been chosen as the category representative because shorter chain molecules are usually regarded as more toxic when compared to structural analogues with longer carbon chain lengths. The 13-week study on 1-hexanol by (Sc. Assoc. 1966) has been used as the key study for the alcohol components of Alchisor TAL 145.

In addition supporting information is provided for tetradecan-1-ol which states that members of the aliphatic alcohol category (C6-C22 as defined in the Long Chain Alcohols SID Initial Assessment Report (SIAM 2006)) are not expected to impair fertility. This conclusion is based on a weight of evidence approach using data from reproductive screening studies (C12 (dodecan-1-ol), C18 (octadecanol)), a fertility study (C22 (docosanol), together with a lack of effect on the reproductive organs in sub-chromic repeat dose studies over the range of linear and essentially linear alcohols. Based on this it is concluded that both dodecan-1-ol and tetradecan-1-ol is not expected to impair fertility.

 

The most sensitive study identified across the constituents of Alchisor TAL 145 for reproductive toxicity has been reported in a study with Hydrocarbons C11-C14, n-alkanes, isoalkanes, cyclics, aromatics (2-25%) with an inhalation NOAEC >300ppm (equivalent to 1720mg/m3). This reliable (Klimisch score 1) OECD 421 comparable study reported pregnancy rates, implantation rate, and implantation efficiency as comparable between exposure groups and negative controls. Studies evaluated for both dodecan-1-oland tetradecan-1-olhave reported endpoints that are less sensitive. As a consequence of this study information Alchsior TAL 145 is determined to have a NOAEC for reproductive screening >300ppm.


Short description of key information:
The most sensitive endpoint for reproduction toxicity has been determined in an inhalation administration reproduction/developmental toxicity screening test (OECD 421) with C9-C14 aliphatics (2-25% aromatic) hydrocarbons fluids. In reliable study (Klimisch score 1) a NOAEC for reproductive toxicity was >300ppm (1720mg/m3). It should be noted that the test item did not induce reproductive toxicity in the offspring or the parental animals.

Effects on developmental toxicity

Description of key information
The most sensitive endpoint for developmental toxicity has been determined in an inhalation administration reproduction/developmental toxicity screening test (OECD 421) with C9-C14 aliphatics (2-25% aromatic) hydrocarbons fluids. In reliable study (Klimisch score 1) a NOAEC for developmental toxicity was >300ppm (1720mg/m3).
Additional information

Alchisor TAL 145 can be characterised according to three constituents: Hydrocarbons C11-C14, n-alkanes, isoalkanes, cyclics, aromatics (2-25%), dodecan-1-ol and tetradecan-1-ol. As defined in the Read-Across Justification Document in section 13, data provided for these constituents when considered together is representative of Alchisor TAL 145 and suitable for assessment purposes. Study data for each constituent has been evaluated. In a protective approach the most sensitive study result from across the three constituents has been identified and used to address the hazard endpoint in question.

 

As detailed in Table 1 below, 7 developmental toxicity related study reports are available for constituents of Alchisor TAL 145. Adequate reliable data is represented for each constituent. Therefore using our protective approach the dataset is a reliable adequate basis for Alchisor TAL 145 assessment purposes.

 

Table 1:Developmental Toxicity Key/Supporting Studies for Constituents of Alchisor TAL 145

 

 

Constituents of Alchisor TAL 145

 

Reference

Hydrocarbons C11 -C14, n-alkanes, isoalkanes, cyclics, aromatics (2 -25%)

Dodecan-1-ol

Tetradecan-1-ol

Hansen 1992

 

Key

Key (read across)

Global ICCA 2005

 

 

Supporting

Exxon 1979

Key

 

 

 

Hydrocarbons C11-C14, n-alkanes, isoalkanes, cyclics, aromatics (2-25%)

 

Hydrocarbons C11-C14, n-alkanes, isoalkanes, cyclics, aromatics (2-25%) are not developmental toxicants. In a developmental study, pregnant dams were exposed by inhalation to 0, 100, or 300ppm test atmospheres of Hydrocarbons C11-C14, n-alkanes, isoalkanes, cyclics, aromatics (2-25%) fluids during gestational days 6 through 15.  No adverse maternal or foetal effects were noted at any dose level. Thus, Hydrocarbons C11-C14, n-alkanes, isoalkanes, cyclics, aromatics (2-25%) fluids did not produce any maternal or foetal toxicity or any developmental effects in rats. Based on the study results, the maternal and developmental toxicity NOAEL is >300 ppm. Based on this study and the lack of systemic toxicity, Hydrocarbons C11-C14, n-alkanes, isoalkanes, cyclics, aromatics (2-25%) fluids, are not expected to be developmental toxicants.

 

Dodecan-1-ol

 

A combined repeat dose and reproductive/developmental toxicity screening study reported a lack of effects on the reproductive organs of male and female rats receiving dodecan-1-ol (NOAEL > 2000 mg/kg/bw) (Hansen 1992, Klimisch 2). This study also reported a NOAEL for developmental effects to be 2000 mg/kg/bw. A read across feeding study reported a lack of effects on the reproductive organs of rats receiving 1 -hexanol (NOAEL 1127 mg/kg) (Scientific Associates Inc., 1966, Klimisch 2). No adverse effects were noted at any of the dose levels administered during the study. Based on the weight of evidence from other alcohols across the category and this reliable screening study it is concluded that dodecan-1-ol is unlikely to be a developmental toxicant in the absence of maternal toxicity.

 

Tetradecan-1-ol

 

On the basis of the weight of evidence from other alcohols across the category and the read across screening study with dodecan-1-ol, (Hansen 1992, Klimisch 2) it is concluded that tetradecan-1-ol is unlikely to be a developmental toxicant in the absence of maternal toxicity. Chronic and sub-chronic toxicity studies have shown that long chain alcohols (LCA) are of low toxicity. Furthermore, combined repeated-dose studies with developmental endpoints, as well as reproductive and developmental studies showed no effects at the highest dose tested.

The most sensitive study identified across the constituents of Alchisor TAL 145 for developmental toxicity has been reported in a study with Hydrocarbons C11-C14, n-alkanes, isoalkanes, cyclics, aromatics (2-25%) with an inhalation NOAEC >300ppm (equivalent to 1720mg/m3). This reliable (Klimisch score 1) OECD 421 comparable study reported no adverse effects due to exposure to the test substance in either dams or foetuses. No treatment related malformation effects were noted in the foetuses. Studies evaluated for both dodecan-1-ol and tetradecan-1-ol have reported endpoints that are less sensitive. As a consequence of this study information Alchsior TAL 145 is determined to have a NOAEC for developmental screening >300ppm.

Justification for classification or non-classification

These findings do not warrant classification of Alchisor TAL 145 as a reproductive or developmental toxin under the new Regulation (EC) 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.