Alcohols, C16-18, ethoxylated, phosphates

Endpoint summary

Description of key information

Oral, subacute:
according to OECD TG 422 in rats: 
systemic NOAEL=800 mg/kg bw/d (highest dose tested) (NOAEL = 660 mg/kg bw corrected for molecular weight)
local NOAEL=200 mg/kg bw/d (highest dose tested) (NOAEL = 166 mg/kg bw corrected for molecular weight)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 2) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional group(s) and similarities in physicochemical and/or (eco)toxicological properties (refer to endpoint discussion for further details).

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for grouping of substances and read-across

There are no data available for repeated dose toxicity ofAlcohols, C16-18, ethoxylated, phosphates(CAS 106233-09-4). In order to fulfil the standard information requirements set out in Annex VIII in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, 1.5, of Regulation (EC) No 1907/2006, whereby physicochemical, toxicological and ecotoxicological properties may be predicted from data for reference substance(s) by interpolation to other substances on the basis of structural similarityPoly(oxy-1,2-ethanediyl), .alpha.-hydro-.omega.-hydroxy-, mono-C8-10 (even numbered)-alkyl ethers, phosphates(CAS 68130-47-2) andPoly(oxy-1,2-ethanediyl), .alpha.-hydro-.omega.-hydroxy-, mono-C11-14-isoalkyl ethers, C13-rich, phosphates (CAS 78330-24-2)are selected as source substances for assessment of repeated dose toxicity.

Repeated dose toxicity

	Target substance (a)	Source substances (b)
CAS	106233-09-4	68130-47-2	78330-24-2
Chemical name	Alcohols, C16-18, ethoxylated, phosphates	Poly(oxy-1,2-ethanediyl), .alpha.-hydro-.omega.-hydroxy-, mono-C8-10 (even numbered)-alkyl ethers, phosphates	Poly(oxy-1,2-ethanediyl), .alpha.-hydro-.omega.-hydroxy-, mono-C11-14-isoalkyl ethers, C13-rich, phosphates
MW	322.42 – 867.27 g/mol	444.51 g/mol	500.62 g/mol
Repeated dose toxicity, oral	RA: CAS 68130-47-2; CAS 78330-24-2	Experimental result: NOAEL systemic = 800 mg/kg bw/day NOAEL local = 200 mg/kg bw/day	Experimental result: NOAEL systemic = 800 mg/kg bw/day NOAEL local = 200 mg/kg bw/day

(a) The substance subject to the REACh Phase-in registration deadline of 31 May 2013 is indicated in bold font.

(b) Reference (read-across) substances are indicated in normal font.

The read-across is mainly based on similar precursers/breakdown products of the target and the source substances. The available endpoint information is used to predict the repeated dose toxicity forAlcohols, C16-18, ethoxylated, phosphates(CAS 106233-09-4).

A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Discussion

A combined repeated dose toxicity study with the reproduction/developmental toxicity screening test was performed withPoly(oxy-1,2-ethanediyl), .alpha.-hydro-.omega.-hydroxy-, mono-C8-10 (even numbered)-alkyl ethers, phosphates(CAS 68130-47-2) according to OECD 422 and in compliance with GLP (CRL, 2009a). This study was chosen as most appropriate study based on the additional information given regarding maternal toxicity in the range finding study. In the range-finding study rats were dosed with 100, 300, and 1000 mg/kg bw/d. At Day 6 the high dose of 1000 mg/kg bw was lowered to 750 mg/kg bw/d, due to excessive toxicity. Reductions of the body weight were observed within Days 4-5. In the gestation period body weights were only slightly reduced in the 300 and 750/1000 mg/kg bw/d dose groups. The female animal of the 1000 mg/kg bw/d group was sacrificed on study Day 4. The animal lost a total of 28 g of body weight and consumed an average of 8 g of food per day. Clinical signs including excess salivation, rales, cold/warm to touch, hunched posture, and scant feces were noted. Necropsy revealed two black ulcerations present in the pyloric region of the stomach, dark red lobes of the liver, red lobes of the lungs, and intestines were distended with gas. Thus, doses of 25, 50, 200, and 800 mg/kg bw/d were chosen for the main study.

In the main study 10 male and female Crj: CD(SD) rats per dose were treated by gavage with 25, 50, 200, and 800 mg/kg bw/d of the test substance. Male rats were dosed once daily for 45 days. The females were treated from Day 14 before mating to Day 4 of lactation, resulting in 38 to 52 dosages. One female rat of the 800 mg/kg bw/d dose group was sacrificed due to adverse clinical observations and two more female rats were found dead due to an intubation error. A decreased body weight gain and decreased food consumption was observed in the animals of the 800 mg/kg bw/d dose group. Local effects were observed in the non-glandular stomach of all animals, including hyperplasia and hyperkeratosis and focal ulceration in 3 males. No effects on haematology, clinical chemistry, neurobehaviour, and organ weights were observed. Based on the effects observed in the high dose group a local NOAEL of 200 mg/kg bw/d was determined. The systemic NOAEL was determined to be 800 mg/kg bw/d. The effects on body weight gain, food consumption and the clinical signs observed were supposed to be a secondary effect of the irritating/corrosive properties ofPoly(oxy-1,2-ethanediyl), .alpha.-hydro-.omega.-hydroxy-, mono-C8-10 (even numbered)-alkyl ethers, phosphates, as no indications for systemic effects were observed. The corrosive effect on mucous membranes is not surprising as the substance itself is also corrosive to the eye, which may be induced by the surfactant properties and/or the low pH.

For comparison with the target substance a correction for molecular weight was performed in a worst case approach, using the alcohol ethoxylated phosphate with the lowest molecular weight, which is contained in the UVCB substance described by their given properties. For Poly(oxy-1,2-ethanediyl), .alpha.-hydro-.omega.-hydroxy-, mono-C8-10 (even numbered)-alkyl ethers, phosphates (CAS 68130-47-2) a molecular weight of 444.51 g/mol was used, which corresponds to a C9 alcohol ethoxylated phosphate with a degree of ethoxylation of 5. Based on the provided information this reflects the higher molecular weight range of the main constituents of the UVCB substance (EPA, 2009). For Alcohols, C16-18, ethoxylated, phosphates (CAS 106233-09-4) a C16 alcohol ethoxylated phosphate with a degree of ethoxylation of 1 as a minimum a molecular weight of 366.48 g/mol (EPI v4.1) was calculated. After correction for molecular weight with a factor of 0.83 (366.48/444.51), a NOAEL of 660 mg/kg bw/day (systemic) and 166 mg/kg bw/day (local) is calculated for Alcohols, C16-18, ethoxylated, phosphates (CAS 106233-09-4).

 

A further combined repeated dose toxicity study with the reproduction/developmental toxicity screening test performed withPoly(oxy-1,2-ethanediyl), .alpha.-hydro-.omega.-hydroxy-, mono-C11-14-isoalkyl ethers, C13-rich, phosphates(CAS 78330-24-2) according to OECD 422 and in compliance with GLP is available for assessment (CRL, 2009b). 10 male and female Crj: CD(SD) rats per dose were treated by gavage with 25, 50, 200, and 800 mg/kg bw/d of the test substance. Male rats were dosed once daily for 46 days. The females were treated from Day 14 before mating to Day 4 of lactation, resulting in 38 to 43 dosages. One male rat of the 800 mg/kg bw/d dose group was sacrificed due to adverse clinical observations. Clinical signs as excess salivation, chromorhinorrhea, and urine-stained abdominal fur were observed in the high dose group. A decreased body weight gain and decreased food consumption was observed in females of the 800 mg/kg bw/d dose group. Males of the 800 mg/kg bw/d group showed a decreased body weight gain, which was not statistically significant. Local effects were observed in the non-glandular stomach of 3/5 females of the high dose group. No effects on haematology, clinical chemistry, and neurobehaviour were observed. Based on the effects observed in the high dose group a local NOAEL of 200 mg/kg bw/d was determined. Similar to the first study no systemic effects were identified, therefore a systemic NOAEL of 800 mg/kg bw/d was determined.

For comparison with the target substance a correction for molecular weight was performed in a worst case approach, using the alcohol ethoxylated phosphate with the lowest molecular weight, which is contained in the UVCB substance described by their given properties. For Poly(oxy-1,2-ethanediyl), .alpha.-hydro-.omega.-hydroxy-, mono-C11-14-isoalkyl ethers, C13-rich, phosphates (CAS 78330-24-2) a molecular weight of 500.62 g/mol was used, which corresponds to a C13 alcohol ethoxylated phosphate with a degree of ethoxylation of 5. Based on the provided information this reflects the higher molecular weight range of the main constituents of the UVCB substance (EPA, 2009). For Alcohols, C16-18, ethoxylated, phosphates (CAS 106233-09-4) a C16 alcohol ethoxylated phosphate with a degree of ethoxylation of 1 as a minimum, a molecular weight of 366.48 g/mol (EPI v4.1) was calculated. After correction for molecular weight with a factor of 0.73 (366.48/500.62), a NOAEL of 586 mg/kg bw/day (systemic) and 146 mg/kg bw/day (local) is calculated for Alcohols, C16-18, ethoxylated, phosphates (CAS 106233-09-4).

 

Conclusion

Based on the results of the subacute studies with analogue substances a systemic NOAEL of 660 mg/kg bw/d and a local NOAEL of 166 mg/kg bw was determined forAlcohols, C16-18, ethoxylated, phosphates for toxicity after repeated exposure, after correction for molecular weight.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall assessment of quality, duration and dose descriptor level (refer to the endpoint discussion for further details).

Justification for classification or non-classification

Based on read-across from a structurally similar substance following an analogue approach, the available data on the repeated dose oral toxicity of the substance do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.