Butane-1,2-diol

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Explanation for the modification of the dose descriptor starting point:

The substance is well tolerated in an acute inhalation toxicity study in Sprague-Dawley rat  (SPF-Quality) with reported LC50 of 370 mg/L air, the only dose tested. No abnormalities or overt toxicity signs reported (similar or eq. to OECD 403; 1978), the substance does not meet the classification for acute inhalation toxicity in accordance to Regulation (EC) No 1272/2008 (CLP) and therefore, no DNEL is required.

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - workers

In (OECD 422, 1992) the systemic toxicity and potential adverse effects was investigated in oral gavage administration of the substance to rats at dosage of 40, 200, and 1000 mg/kg.  Food consumption mean body weights and body weight gain were unaffected in all treated groups.  No mortality was observed, body weight, food consumption, haematology and organ weight were unaffected throughout the study.  For glucose in the 40 mg/kg group and total bilirubin in the 200 mg/kg group, statistical differences were noted. However, no related changes suggestive of the effects of the test article were noted.

In females of the 1000 mg/kg group, post-treatment decreases in locomotor activity were observed in more than half of the animals and hypopnea in a few animals. Both signs were transient in nature. The number of affected animals decreased over time, and on day 6 or later, the sign occurred only in one animal until gestation day 5 (at 21 days after the commencement of treatment). No abnormalities occurred in males. In addition, hair loss was observed in one female of the 1000 mg/kg group, but the finding is considered a spontaneous finding.

Bilateral atrophy of the testes was found in one male of the 1000 mg/kg group (animal number: DM09), this was reflected by extensive atrophy of seminiferous tubules found in histopathology and associated with slight bilateral atrophy of the epididymides. In the testes, degeneration, vacuolation, and multinucleate cell formation were observed in the sperm cells, but no abnormalities were observed in Sertoli cells or interstitial cells. In the other animals, including those of the 40 and 200 mg/kg groups, no abnormalities were found in the testes or epididymides. The other changes included germinal centre deficiency in the spleen and unilateral extensive hemorrhagic necrosis in the adrenal cortex in one female of the 1000 mg/kg group (D07).

In both the control group and 1000 mg/kg group, focal myocardial degeneration in the heart, microgranuloma in the liver, fatty change of hepatocytes, and brown pigmentation in tubular epithelial cells, cyst, focal basophilic change in renal tubules and fatty change of tubular epithelia in the kidneys were sporadically found. No between-group differences in the incidences of these changes were noted; therefore, these changes were not indicative of the treatment effects. In addition, in females, slight increases of hematopoietic cells in the spleen and diffuse chronic hypertrophy in the fascicular zone of the adrenals were found in almost all animals in the control and 1000 mg/kg groups without any between-group differences.

Reproductive performance for both males and females, there were no abnormalities noted in copulation index or fertility index, and no effect of the test article was noted in gestation length, delivery, or nursing behaviour. Furthermore, the examination on corpora lutea count, implantation site count, implantation index, gestation index, delivery index, offspring count, and viable offspring count revealed no changes suggestive of effects of the test article on ovulation, implantation, or subsequent embryonic development. In addition, no abnormality was noted in the external surface of the offspring, viability index, bodyweight at birth, or bodyweight gain after birth. In necropsy of neonates, thymic remnant in the neck and left umbilical artery were sporadically found. However, these findings were those often spontaneously observed at the end of the fetal stage, and the incidences were not correlated with dose levels. In one female of the 1000 mg/kg group, (a) white spot(s) was(were) found, which was (were) hepatic necrosis and fatty change. These changes are known to be induced by various factors, and it is widely recognised that these changes are also induced by circulatory impairment and metabolic disorder including nutritional disorder. In this study, however, the changes occurred in only one animal and were not found in the other neonates; therefore, they were not considered treatment related.

Therefore, the no observed adverse effect levels (NOAEL) under the experimental conditions used were considered 1000 mg/kg for repeat dose toxicity, reproductive and developmental toxicity.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Explanation for the modification of the dose descriptor starting point:

The substance is well tolerated in an acute inhalation toxicity study in Sprague-Dawley rat  (SPF-Quality) with reported LC50 of 370 mg/L air, the only dose tested. No abnormalities or overt toxicity signs reported (similar or eq. to OECD 403; 1978), the substance dis not meet the classification for acute inhalation toxicity in accordance to Regulation (EC) No 1272/2008 (CLP) and therefore, no DNEL is required.

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - General Population

In (OECD 422, 1992) the systemic toxicity and potential adverse effects was investigated in oral gavage administration of the substance to rats at dosage of 40, 200, and 1000 mg/kg.  Food consumption mean body weights and body weight gain were unaffected in all treated groups.  No mortality was observed, body weight, food consumption, haematology and organ weight were unaffected throughout the study.  For glucose in the 40 mg/kg group and total bilirubin in the 200 mg/kg group, statistical differences were noted. However, no related changes suggestive of the effects of the test article were noted.

In females of the 1000 mg/kg group, post-treatment decreases in locomotor activity were observed in more than half of the animals and hypopnea in a few animals. Both signs were transient in nature. The number of affected animals decreased over time, and on day 6 or later, the sign occurred only in one animal until gestation day 5 (at 21 days after the commencement of treatment). No abnormalities occurred in males. In addition, hair loss was observed in one female of the 1000 mg/kg group, but the finding is considered a spontaneous finding.

Bilateral atrophy of the testes was found in one male of the 1000 mg/kg group (animal number: DM09), this was reflected by extensive atrophy of seminiferous tubules found in histopathology and associated with slight bilateral atrophy of the epididymides. In the testes, degeneration, vacuolation, and multinucleate cell formation were observed in the sperm cells, but no abnormalities were observed in Sertoli cells or interstitial cells. In the other animals, including those of the 40 and 200 mg/kg groups, no abnormalities were found in the testes or epididymides. The other changes included germinal centre deficiency in the spleen and unilateral extensive hemorrhagic necrosis in the adrenal cortex in one female of the 1000 mg/kg group (D07).

In both the control group and 1000 mg/kg group, focal myocardial degeneration in the heart, microgranuloma in the liver, fatty change of hepatocytes, and brown pigmentation in tubular epithelial cells, cyst, focal basophilic change in renal tubules and fatty change of tubular epithelia in the kidneys were sporadically found. No between-group differences in the incidences of these changes were noted; therefore, these changes were not indicative of the treatment effects. In addition, in females, slight increases of hematopoietic cells in the spleen and diffuse chronic hypertrophy in the fascicular zone of the adrenals were found in almost all animals in the control and 1000 mg/kg groups without any between-group differences.

Reproductive performance for both males and females, no abnormality was noted in copulation index or fertility index, and no effect of the test article was noted in gestation length, delivery, or nursing behaviour. Furthermore, the examination on corpora lutea count, implantation site count, implantation index, gestation index, delivery index, offspring count, and viable offspring count revealed no changes suggestive of effects of the test article on ovulation, implantation, or subsequent embryonic development. In addition, no abnormality was noted in the external surface of the offspring, viability index, bodyweight at birth, or bodyweight gain after birth. In necropsy of neonates, thymic remnant in the neck and left umbilical artery were sporadically found. However, these findings were those often spontaneously observed at the end of the fetal stage, and the incidences were not correlated with dose levels. In one female of the 1000 mg/kg group, (a) white spot(s) was(were) found, which was (were) hepatic necrosis and fatty change. These changes are known to be induced by various factors, and it is widely recognised that these changes are also induced by circulatory impairment and metabolic disorder including nutritional disorder. In this study, however, the changes occurred in only one animal and were not found in the other neonates; therefore, they were not considered treatment related.

Therefore, the no observed adverse effect levels (NOAEL) under the experimental conditions used were considered 1000 mg/kg for repeat dose toxicity, reproductive and developmental toxicity.