Propanoic acid, 2-hydroxy-, 2-ethylhexyl ester, (2S)-

Carcinogenicity

Description of key information

No data is available for the 2-ethylhexyl-S-lactate itself. Therefore, available data from carcinogenicity studies in mice and rats study conducted with a suitable read-across partner was used to assess the carcinogenic potential of the target substance. Based on the results, no classification for carcinogenicity is warranted for 2-ethylhexyl-S-lactate.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

carcinogenicity: oral

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

For details and justification of read-across please refer to the attached report in section 13 of IUCLID.

Reason / purpose for cross-reference:

read-across source

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Clinical observations related to treatment with 2-ethylhexanol were limited to dose-related increases in the number of rats in poor general condition, defined as lethargy and unkemptness, and with labored breathing. The incidence of poor general condition (number of daily observations per number of affected rats) in vehicle control males was 62/12 and in females 34/8 and of labored breathing in males 2/1 and in females 9/3. At 500 mg/kg the incidence of poor general condition in males was 200/14 and in females 248/41 and of labored breathing in males was 41/4 and in females 75/12.

Dermal irritation (if dermal study):

not examined

Mortality:

mortality observed, treatment-related

Description (incidence):

Mortality was moderate in the rat during the first 78 weeks of dosing except for females at 500 mg/kg. A considerable increase in mortality in rats occurred in control and treatment groups between 78 weeks and final sacrifice. Mortalities in male rats were not dose-related; the 38 % mortality at 500 mg/kg was exceeded by that at 50 mg/kg (46 %). The mortality increase at 500 mg/kg in females was clearly dose-related and amounted to 52% of the animals in the group.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Treatment-related reductions in weight gain compared with controls occurred for both sexes. At the end of treatment statistically significant differences from vehicle controls were: males -5 % at 50 mg/kg, -11 % at 150 mg/kg, and -23 % at 500 mg/kg; females -9 % at 150 mg/kg and -21 % at 500 mg/kg.There were no statistically significant differences in body weight gain between water and vehicle controls for female rats. There was a slight decrease in body weight for male water control rats compared with male vehicle controls, amounting to 1.5–5.0 % at intervals throughout the dosing period. This difference is considered to be biologically unimportant.
Male and female rats showed no overall differences in food consumption from vehicle controls at any dose level.

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

There were no treatment-related differences in rats after 12, 18, and 24 months. In male rats at 500 mg/kg there were slight morphological changes in red cells at 12 months only, manifested as an increased incidence of anisocytosis (9/46 animals), predominantly as microcytosis (5/46 animals). These changes were not observed in controls.

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

In the rat the only change in relative organ weight at 50 mg/kg was a small statistically significant increase in relative female stomach weight (6 %). There were statistically significant increases in relative organ weights, expressed as percentage of vehicle control, in the rat at 150 mg/kg (stomach, M 7 % and F 9 %; liver, F 11 %; kidneys, M 22 % and F 7 %; brain, M and F 19 %) and at 500 mg/kg (stomach, M 21 % and F 20 %; liver, F 13 %; kidneys, M 19 % and F 14 %; brain, M 19 % and F 18 %; testis, 21 %). There were no changes in relative spleen weight at any dose level. There were no statistically significant differences in relative organ weights between water and vehicle controls.See also table 1 in "Any other information on results incl. tables)".

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

There were moderate increases in the incidence of focal lesions and discolorations in the lung in male and female rats at the high dose. These were in water controls, males 10 %, females 6 %; in vehicle controls, males 8 %, females 14 %; at 50 mg/kg, males 14 %, females 8 %; at 150 mg/kg, males 12 %, females 18 %; and at 500 mg/kg, males 26 %, females 30 %. There was a moderate incidence of focal lesions and discolorations in the glandular stomach of male rats, not related to treatment. In all female rats the incidence of such lesions was 14 % in water controls, 12 % in vehicle controls, 12 % at 50 mg/kg, 18 % at 150 mg/kg, and 28 % at 500 mg/kg.

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

There was an increased incidence of basophilic foci in female decedents at 50 mg/kg (50 %) compared with controls (12 %); however, in all females at 50 mg/kg there was no difference from controls and no differences in any other female or male treatment group. There were significant increases in hepatic congestion in decedents at 500 mg/kg (M, 74 %; F, 88 %) compared with vehicle controls (M, 31 %; F, 29 %) but not in survivors. Hepatic peripheral fatty infiltration was elevated in all female rats at 50 mg/kg (56 %) compared with vehicle (34 %) controls; since there was no increase at any other dose level in decedents or survivors, this increase was probably incidental. Hepatic peripheral fatty infiltration was unaltered in treated males. Microscopically, the gross focal lesions and discolourations in the glandular stomach of both male and female rats appeared as erosions, ulcers, horny or glandular cysts, or focal lymphoid infiltrations. They were not considered to be neoplastic. There were no differences from controls in the extent of erosion and ulceration in female rats; the increased incidence of gross findings at 50 mg/kg is considered to be without significance. The increase of ulceration in males at 50 mg/kg was not accompanied by increases at higher doses and is probably without significance. There were no microscopic findings differing from controls in the forestomachs of treated male or female rats and none in the female glandular stomach. There was a marked increase in lung congestion in male rat decedents at 500 mg/kg (58 %) compared with controls (8 %) and in female rat decedents at 150 mg/kg (46 %) and 500 mg/kg (69 %), compared with controls (4 %). The gross focal lesions in the lung appeared microscopically as multifocal pneumonia or as foam cell aggregates and were not neoplastic. There was an increased incidence of bronchopneumonia at 500 mg/kg (M, 28 %; F, 30 %) compared with controls (M, 10 %; F, 6 %). Several animals with bronchopneumonia had small foreign body particles in the lungs, and the bronchopneumonia may have been aspiration induced. The slight increase of foam cells in males at 500 mg/kg (18 %) compared with controls (4 %) is of marginal significance since it is absent from females at the same dose level. While the incidence of haemosiderin storage in vehicle control spleens was quite high (M, 64 %; F, 72 % of animals), there was an increased incidence at 500 mg/kg in female rats (88 %). This was attributed to the lower number of animals with infiltrates of malignant lymphoma cells in the high-dose group. A lower rate of replacement of phagocytes by lymphoma cells would increase the possibility of hemosiderin storage. Mesenteric and mandibular lymph node hyperplasia was increased over controls in all female rats and in male decedents at 500 mg/kg. A small increase in the incidence of prostatic atrophy was seen in all male rats at 500 mg/kg. Female rat decedents exhibited an increased incidence in congestion (62 %) and calcification (65 %) in the kidneys at 500 mg/kg and in calcification (69 %) at 150 mg/kg compared with decedent controls (congestion, 29 %;calcification, 5 %); however, when female survivors were included these incidences did not differ from controls.

Histopathological findings: neoplastic:

no effects observed

Description (incidence and severity):

There were no significant differences compared to the vehicle controls in the incidence of liver adenomas in males or females and in the incidence of hepatocellular carcinomas in survivors or in prior decedants in any treated group, when compared by Fisher's exact test. Hepatocellular data for males and females showed no adverse trend at p < 0.01 when tested by the time-independent simple Peto and Cochran-Armitage tests against vehicle controls. Male rats showed a slight adverse trend at p < 0.05 in the simple Peto test against vehicle controls, but not in the Cochran-Armitage test. There was no adverse trend in male or female hepatocellular carcinoma data when tested against vehicle controls in the time-dependent Peto test.

Details on results:

There were no dose-related changes at 50 mg/kg. There was reduced body weight gain at 150 mg/kg (M, 16; F, 12 %) and 500 mg/kg (M, 33; F, 31 %) and an increased incidence of lethargy and unkemptness. There were dose-related increases in relative liver, stomach, brain, kidney, and testis weights at sacrifice. Female rat mortality was markedly increased at 500 mg/kg. There was marked aspiration-induced bronchopneumonia in rats at 500 mg/kg; hematologic, gross, and microscopic changes, including tumors, were otherwise comparable among all rat groups.

Relevance of carcinogenic effects / potential:

2-ethylhexanol is not carcinogenic in rats.

Key result

Dose descriptor:

NOAEL

Effect level:

500 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: absence of neoplastic lesions

Remarks on result:

other: Effect type: carcinogenicity

Key result

Dose descriptor:

LOAEL

Effect level:

500 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

mortality

Remarks on result:

other: Effect type: toxicity

Key result

Dose descriptor:

NOAEL

Effect level:

150 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

mortality

Remarks on result:

other: Effect type: toxicity

Critical effects observed:

not specified

Table 1: Relative organ weights at sacrifice for rats receiving 2-ethylhexanol

Dose (mg/kg/day)	Water control	Vehicle control	50	150	500
Males
Stomach	0.60	0.58	0.59	0.62**	0.70**
Liver	3.69	3.53	3.47	3.96	3.85
Kidneys	0.89	0.76	0.8	0.85**	0.93**
Spleen	0.85	0.56	0.44	0.86	0.59
Brain	0.62	0.60	0.62	0.66**	0.72**
Testis	1.47	1.38	1.22	1.39	1.66**
Females
Stomach	0.66	0.66	0.70*	0.72**	0.79**
Liver	3.69	3.49	3.68	3.89**	3.94**
Kidneys	0.81	0.82	0.83	0.88**	0.94**
Spleen	0.53	0.47	0.41	0.69	0.30
Brain	0.77	0.77	0.78	0.84**	0.91**

Values are organ/body wt at necropsy. Values in bold differ from vehicle controls.

*Statistically different at p < 0.05.

** Statistically different at < 0.01.

Conclusions:

2-ethylhexanol was not carcinogenic in the Fischer F344 rat.

Executive summary:

In a carcinogenicity study equivalent to OECD 451, 2-ethylhexanol was administered to 50 Fischer F344 rats/sex/dose in an aqueous Chromophor EL solution at dose levels of 0, 50, 150, and 500 mg/kg for 24 months.

2-ethylhexanol was not oncogenic in the Fischer F344 rat in a valid GLP carcinogenicity study (Astill et al., 1996). In both sexes the sum of primary tumours, the sum of benign tumours and the sum of malignant tumours was lower in the top dose group than in either the vehicle control or the water control groups. A dose related increase in mortality was observed in female rats, with 52 % mortality in those given 500 mg/kg bw/d. Dose related reductions in weight gain were observed. Increased focal lesions and lung discolouration was observed in rats at 500 mg/kg bw/d. The 50 mg/kg bw/d dose produced a 6 % increase in relative female stomach weight. Significant increases in stomach, kidney and brain relative weights were observed in male rats at 150 mg/kg bw/d with testis relative weight increase at 500 mg/kg bw/d. Female rats had significantly increased stomach, liver, kidney and brain relative weights at the 150 and 500 mg/kg bw/d doses.

At the doses tested, there was not a treatment related increase in tumour incidence when compared to controls. Therefore, the NOAEL for carcinogenicity is 500 mg/kg bw/d based on this study.

The NOAEL for toxic effects is 150 mg/kg bw/d (corresponding to 234 mg/kg bw/d 2-ethylhexyl-S-lactate).

This carcinogenicity study in the rat is acceptable and the guideline requirement for a carcinogenicity study (OPPTS 870.4200; OECD 451) in rats.

This information is used in a read-across approach in the assessment of the target substance.

For justification of read-across please refer to the attached read-across report (see IUCLID section 13).

Reference 2

Endpoint:

carcinogenicity: oral

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

For details and justification of read-across please refer to the attached report in section 13 of IUCLID.

Reason / purpose for cross-reference:

read-across source

Clinical signs:

no effects observed

Description (incidence and severity):

There were no instances of poor general condition and labored breathing in mice related to treatment with 2-ethylhexanol.

Dermal irritation (if dermal study):

not examined

Mortality:

mortality observed, treatment-related

Description (incidence):

In mice, mortality in controls and at 50 and 200 mg/kg/day was generally low throughout. There was a marked increase in male and female mortality at 750 mg/kg/day, with an early onset. This high mortality by 78 weeks in both sexes at 750 mg/kg made it inadvisable to extend the dosing period further. Therefore, dosing was terminated during weeks 79 through 81 and mice were sacrificed and necropsied. There were no differences between vehicle and water control mortality rates in either rats or mice. See for cumulative percentage incidences of spontaneous deaths and moribund sacrifices Table 1 in "Any other information on results incl. tables".

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Treatment-related reductions in weight gain compared with controls occurred for both sexes. Differences from vehicle controls were: males -5 % at 200 mg/kg and -1 2% at 750 mg/kg; and females -14 % at 750 mg/kg. There were no statistically significant differences in body weight gain between water and vehicle controls male and female mice.
There was a statistically significant decrease in food intake by mice at 750 mg/ kg/day, compared with vehicle controll. This amounted to -9 % (males) and -12 % (females) over the course of treatment.

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Description (incidence and severity):

There were no treatment-related differences between treatments and controls in red cell morphology in mice after 12 and 18 months. There were slight increases in neutrophils at 750 mg/kg in mice at 12 months (males 33 %, females 17 %) and at 18 months (males 31 %) and slight decreases in lymphocytes at 12 months (males 10 %, females 5 %) and at 18 months (males 8 %) compared with controls.

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

In the mouse there were no changes in relative organ weights at 50 and 200 mg/kg, with the exception of small increases in relative testis weights of 7 % at 50 mg/kg and 5 % at 200 mg/kg. Significant organ weight increases in the mouse were mostly limited to 750 mg/kg (stomach, M 16 % and F 19 %; liver, F 21 %; kidney, F 13 %; brain, M 7 % and F 12 %; testis 13 %). There were no changes in relative spleen weight at any dose level. There were no statistically significant differences in relative organ weights between water and vehicle controls. See also Table 1 in "Any other information on results incl. tables)".

Gross pathological findings:

no effects observed

Description (incidence and severity):

There were no dose-related differences from controls in the incidence of lung or stomach focal lesions in mice treated with 2-ethylhexanol and no other treatment related differences from controls.

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

There were no significant treatment-related differences between treatments and controls in the mouse fore- or glandular stomach in decedents or survivors. There was a significant increase in the incidence of lung congestion in all mice at 750 mg/kg (M, 18 %; F, 20 %) compared with controls (M, 2 %; F, 4 %). Most of the increase occurred in prior decedents. There was an increased incidence of liver congestion in males at 750 mg/kg (14 %) compared with controls (0 %), accounted for entirely by decedents, but there was no increase in the incidence of liver congestion in any female treated group. Hepatic peripheral fatty infiltration was increased at 750 mg (M, 62 %; F, 44 %), compared with controls (M, 0 %; F, 0 %), an increase seen predominantly in survivors. There were no hepatic basophilic foci in male and female control or treated decedents. There were small but significant increases in the incidence of hepatic basophilic foci in male survivors at 200 mg/kg (24 %) compared with controls (8 %) and in female survivors at 750 mg/kg (12 %) compared with controls (2 %). There was an apparently anomalous increase in the incidence of focal hyperplasia in females at 200 mg/kg, but not at any other treatment level, and no significant differences from controls in focal hyperplasia in male mice.

Histopathological findings: neoplastic:

effects observed, treatment-related

Description (incidence and severity):

There were no treatment-related differences between treatments and controls in the incidence of liver adenomas in male or female mice. When hepatocellular carcinoma incidence data were analyzed using Fisher's exact test there were no treatment related differences from vehicle controls in male mice, and a statistically significant increase only at 750 mg/kg in female mice (5/50, 10 %, p < 0.05), compared with vehicle controls, but not with water controls. In view of the decreased body weight and relatively high mortality at 750 mg/kg in males and females, hepatocellular carcinoma data sets consisting of control and low and middle dose levels, and of control and all treatment levels, were tested for an adverse trend. When all treatment groups were compared with vehicle controls using time-independent tests, there was an adverse trend in female mice in the simple Peto (p < 0.01) and Cochran-Armitage (p < 0.05) tests and essentially no trend in male mice. When all treatment groups were compared using the time-dependent Peto test, there were adverse trends in females compared with vehicle controls (p < 0.01) and in males compared with vehicle controls (p < 0.05). When data from low and middle dose levels only were tested there was no adverse trend in males in time-independent or dependent tests against vehicle controls and an adverse trend in female mice only in the simple Peto test compared with vehicle controls (p < 0.05). Male and female hepatocellular carcinoma incidences were adjusted for mortality by fitting vehicle control and treatment data to a multistage Weibull model (second degree in dose) and deriving the hypothetical number of additional carcinomas if all animals had survived to termination and subsequently had been carried to 104 weeks. Adjusted incidence at 750 mg/kg for male mice at 81 weeks (the effective dosing duration for high-dose mouse groups) was 18.8 % and at 104 weeks 19.9 %, compared with an unadjusted incidence of 18 %. Adjusted incidence at 750 mg/kg for female mice at 81 weeks was 13.1 % and at 104 weeks 19.3 %, compared with an unadjusted incidence of 10 %. There were no metastases from the hepatocellular carcinomas and no other treatment-related differences from controls in tumour incidence for any other organ in surviving or deceased male or female mice. Water and vehicle control animals gave closely similar microscopic findings, with the exceptions of slightly decreased glandular stomach erosion and mandibular lymph node hyperplasia in female rat water controls and of slightly decreased liver focal hyperplasia in male mice water controls, compared with vehicle controls.

Other effects:

not specified

Details on results:

Carcinogenicity: 2-ethylhexanol is likely a weak or equivocal carinogen in female mice. In male mice it is considered to be non-carcinogen. There is marked toxicity at the high dose and the survival-adjusted tumour incidence at that dose is within the historical control range.

Relevance of carcinogenic effects / potential:

There was a 12 % incidence of hepatic basophilic foci and an 18 % incidence of hepatocellular carcinomas in male mice at 750 mg/kg, not statistically significant compared with either control by Fisher's exact test. There was a 12 % incidence of hepatic basophilic foci and a 10 % incidence of hepatocellular carcinomas in female mice at 750 mg/kg, statistically significant (p < 0.05) compared with vehicle control, but not signficiant when compared with water controls by Fisher's exact test. There were no metastases. Time-dependent and -independent statistical analyses showed an adverse trend in the incidence of hepatocellular carcinomas in male and female mice, correlated with toxicity (expressed as mortality) at 750 mg/kg. The time-adjusted incidence of hepatocellular carcinomas in male mice (18.8 %) was within the historical normal range at the testing facility (0–22 %), but that in females (13.1 %) was outside the normal range (0–2 %).
In conclusion there are weak adverse trends in hepatocellular carcinoma incidence in mice at high dose levels which may have been associated with toxicity.

Key result

Dose descriptor:

NOAEL

Effect level:

750 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: absence of neoplastic effects

Remarks on result:

other: Effect type: carcinogenicity

Key result

Dose descriptor:

LOAEL

Effect level:

750 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

mortality

other: hepatotoxicity

Remarks on result:

other: Effect type: toxicity

Key result

Dose descriptor:

NOAEL

Effect level:

200 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

histopathology: non-neoplastic

Remarks on result:

other: Effect type: toxicity

Critical effects observed:

not specified

Table 1: Relative organ weights at sacrifice for rats receiving 2-ethylhexanol

Dose (mg/kg/day)	Water control	Vehicle control	50	150	500
Males
Stomach	0.85	0.86	0.84	0.89	1.0**
Liver	4.30	4.30	4.01	4.42	4.77
Kidneys	2.04	2.01	2.04	1.93	1.84**
Spleen	0.21	0.21	0.20	0.21	0.19
Brain	1.35	1.33	1.38	1.36	1.43**
Testis	0.63	0.61	0.65**	0.64*	0.69**
Females
Stomach	0.91	0.94	0.94	0.97	1.11**
Liver	3.67	3.75	3.79	4.08	4.54**
Kidneys	1.27	1.28	1.28	1.28	1.44**
Spleen	0.35	0.46	0.37	0.37	0.32
Brain	1.37	1.41	1.43	1.41	1.57**

Values are organ/body wt at necropsy. Values in bold differ from vehicle controls.

*Statistically different at p < 0.05.

** Statistically different at < 0.01.

Conclusions:

2-ethylhexanol is not carcinogenic in the male B6C3F1 mouse. A weak adverse trend in increased liver carcinoma incidence was attributed to the toxicity of 2-ethylhexanol at the high dose level. This is supported by the observation that liver carcinoma were seen at a high rate (50 %) in decedents.

Executive summary:

In a carcinogenicity study equivalent to OECD 451, 2-ethylhexanol was administered to 50 B6C3F1 mice/sex/dose in an aqueous Chromophor EL solution at dose levels of 0, 50, 200, and 750 mg/kg for 18 months.

At the top dose of 750 mg/kg bw/d 2-ethylhexanol caused a reduction of body weight gain in both sexes at early stages of the study (approx. from study, week 6 onwards), a reduced terminal body weight, and an increased mortality of up to approx. 30 % in week 78. Relative organ weight changes were mostly limited to the top dose groups as evidenced by statistically significantly increased relative weights of the stomach, liver, brain and testes in males, and of the stomach, liver, kidneys and brain in females. No neoplastic lesions were seen in males. In top dose females, the incidence of hepatocellular lesions was significantly increased, but this was attributed to the toxicity that was associated with the high dose (750 mg/kg bw/d). This was supported by the observation that the incidence of liver carcinoma was high (50 %) in decedents. The NOAEL (carcinogenicity) was therefore 750 mg/kg bw/d in male and female mice. The NOAEL for systemic toxicity was 200 mg/kg bw/d in this study (Astill et al., 1996). At the doses tested, there was not a treatment related increase in tumour incidence when compared to controls.

This carcinogenicity study in the mice is acceptable and the guideline requirement for a carcinogenicity study (OPPTS 870.4200); OECD 451 in rodents.

This information is used in a read-across approach in the assessment of the target substance.

For justification of read-across please refer to the attached read-across report (see IUCLID section 13).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

234 mg/kg bw/day

Study duration:

chronic

Species:

rat

System:

other: general toxicity

Organ:

other: unspecific

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the results, no classification for carcinogenicity is warranted in accordance with CLP regulations 1272/2008.

Additional information

The target substance is very quickly enzymatically hydrolysed to ethylhexanol and L(+)-lactic acid, indicating that the compounds systemically available are lactic acid and ethylhexanol. Therefore, the requirements for carcinogenicity shall be addressed based on information for lactic acid and ethylhexanol. Lactic acid is a ubiquitous and integral part of mammalian metabolism and therefore of minor toxicological relevance in comparison to ethylhexanol, which is more important for the toxicological assessment.

No study is available elucidating the carcinogenicity of the target substance. Thus, available carcinogenicity studies conducted with the read-across partner ethylhexanol was used to assess the target substance for any carcinogenic potential. For more details on the read-across justification please refer to IUCLID section 13.

 

In both carcinogenic studies conducted equivalent to OECD 451 with 2-ethylhexanol in mice or rats, there was no treatment related increase in tumour incidence in comparison with controls.