2-hydroxy-1-[4-[4-(2-hydroxy-2-methylpropanoyl)phenoxy]phenyl]-2-methylpropan-1-one

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Version / remarks:

Annex V B.7, OECD n.407

Qualifier:

according to guideline

Guideline:

EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))

Version / remarks:

Annex V B.7, OECD n.407

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

other: Hsd

Route of administration:

oral: unspecified

Vehicle:

other: Water ad inj.

Details on oral exposure:

Method of administration:
Gavage of a suspension, using a stomach tube

Duration of treatment / exposure:

28 days

Frequency of treatment:

7 days/week

No. of animals per sex per dose:

Male: 5 animals at 0 mg/kg bw/day
Male: 5 animals at 5 mg/kg bw/day
Male: 5 animals at 50 mg/kg bw/day
Male: 5 animals at 150 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 5 mg/kg bw/day
Female: 5 animals at 50 mg/kg bw/day
Female: 5 animals at 150 mg/kg bw/day

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

No severe treatment-related clinical signs were observed.

Mortality:

no mortality observed

Description (incidence):

No animals died during the study.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Bodyweight were affected by treatment in male high dose group

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

Food consumption were affected by treatment in male high dose group

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

Some individual haematology deviations were observed but considered not biologically relevant.

Urinalysis findings:

no effects observed

Description (incidence and severity):

No differences between dosed group and control are observed in urine parameters.

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Histopathological findings considered to be direcly treatment-related were observed in the adrenal gland, liver, lung and spleen, in 50 and 150 mg/kg bw dose groups.
After 14 days recover period for High dose group, liver changes were fully reversible and adrenal gland, lung and spleen chenges had almost reversed.

Key result

Dose descriptor:

NOAEL

Effect level:

5 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

food consumption and compound intake

histopathology: non-neoplastic

Key result

Critical effects observed:

no

Lowest effective dose / conc.:

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

Conclusions:

Under the study conditions, the rat 28 d NOEL for systemic effects was considered to be 5 mg/kg bw/day.

Executive summary:

A study was conducted to determine the repeated dose oral toxicity of the test substance according to OECD Guideline 407 and EU Method B.7, in compliance with GLP. Groups of 5 male and female Hsd rats were administered 0, 5, 50 and 150 mg/kg bw/day of test substance by oral gavage for 28 days. There were no treatment-related changes at 5 mg/kg bw/day. No severe treatment-related clinical signs were notede at any dose. Individual haematology deviations were observed but considered not biologically relevant. No significant changes were observed in urine parameters. In the high dose group, feed consumption and body weight were affected in males. Treatment-related histopathological findings were observed in the adrenal gland, liver, lung and spleen, at 50 and 150 mg/kg bw. After 14 days recovery period for the high dose group, liver changes were fully reversible and adrenal gland, lung and spleen changes had almost reversed. Under the study conditions, the rat 28 d NOEL for systemic effects was considered to be 5 mg/kg bw/day (Bioservice, 2007). 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

5 mg/kg bw/day

Study duration:

subacute

Experimental exposure time per week (hours/week):

168

Species:

rat

Quality of whole database:

The information requirement for this tonnage band is sufficiently met with the available data.

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Reason / purpose for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Reason / purpose for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

a short-term toxicity study does not need to be conducted because exposure of humans via the dermal route in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

other:

Reason / purpose for cross-reference:

data waiving: supporting information

Repeated dose toxicity: dermal - local effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

a short-term toxicity study does not need to be conducted because exposure of humans via the dermal route in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

other:

Reason / purpose for cross-reference:

data waiving: supporting information

Additional information

A study was conducted to determine the repeated dose oral toxicity of the test substance according to OECD Guideline 407 and EU Method B.7, in compliance with GLP. Groups of 5 male and female Hsd rats were administered 0, 5, 50 and 150 mg/kg bw/day of test substance by oral gavage for 28 days. There were no treatment-related changes at 5 mg/kg bw/day. No severe treatment-related clinical signs were notede at any dose. Individual haematology deviations were observed but considered not biologically relevant. No significant changes were observed in urine parameters. In the high dose group, feed consumption and body weight were affected in males. Treatment-related histopathological findings were observed in the adrenal gland, liver, lung and spleen, at 50 and 150 mg/kg bw. After 14 days recovery period for the high dose group, liver changes were fully reversible and adrenal gland, lung and spleen changes had almost reversed. Under the study conditions, the rat 28 d NOEL for systemic effects was considered to be 5 mg/kg bw/day (Bioservice, 2007). 

 

Justification for classification or non-classification

Based on the result of a repeated dose oral toxicity study (OECD Guideline 407), the test substance does not warrant classification for this endpoint according to EU CLP criteria (Regulation 1272/2008/ EC).