Solsperse 22000-Wirksubstanz

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Effects of test substance on fertility and developmental toxicity have been investigated in a One generation reproductive toxicity study (OECD 415). No treatment related effects were observed in parental animals or offspring up to the highest concentration tested (1000 mg/kg bw/day) indicating that the test substance do not affect fertility and offspring development.

Link to relevant study records

Reference

Endpoint:

one-generation reproductive toxicity

Remarks:

based on test type (migrated information)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Qualifier:

according to guideline

Guideline:

OECD Guideline 415 [One-Generation Reproduction Toxicity Study (before 9 October 2017)]

Principles of method if other than guideline:

EEC Directive 87/302/EEC, Annex V of the EEC Directive67/548/EEC, Part B: Methods for determination of Toxicology "One-Generation Reproductive Toxicity Test". Official Journal of the European Communities No. L 133, May 1988.OECD "Guidelines for Testing of Chemicals", Section 4,Health Effects, No. 415, "One-Generation Reproductive Toxicity Test", Paris Cedex, September 1983.

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 400

Details on exposure:

Method of administration or exposure: Gavage

Frequency of treatment:

Dosing regime (males): 7 days/weekDosing regime (females): 7 days/week

Details on study schedule:

Number of litters per dose/conc.: 24 at mg/kg or mg/l

Dose / conc.:

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

Dose / conc.:

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

Dose / conc.:

1 000 mg/kg bw/day (actual dose received)

Dose / conc.:

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

Remarks:

Control

No. of animals per sex per dose:

Male: 24 animals at 0 mg/kg or mg/lMale: 24 animals at 50 mg/kg or mg/lMale: 24 animals at 200 mg/kg or mg/lMale: 24 animals at 1000 mg/kg or mg/lFemale: 24 animals at 0 mg/kg or mg/lFemale: 24 animals at 50 mg/kg or mg/lFemale: 24 animals at 200 mg/kg or mg/lFemale: 24 animals at 1000 mg/kg or mg/l

Clinical signs:

no effects observed

Dermal irritation (if dermal study):

not examined

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not specified

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

no effects observed

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not examined

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not examined

Reproductive performance:

no effects observed

Adults males and females tolerated the test substance at oral doses levels up to and including 1000 mg/kg/day without changes to appearance and behaviour and without effect on survival, body weight and food intake.The results of the study indicate that mating was successful in all groups with similar mean coital times recorded for all groups. There was no indication of any treatment related effects on fertility since fertility and conception rateswerer similat for treated and control groups. Gestation times were unaffected by treatment.

Key result

Dose descriptor:

NOAEL

Effect level:

> 1 000 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Remarks on result:

not determinable due to absence of adverse toxic effects

Clinical signs:

no effects observed

Dermal irritation (if dermal study):

not examined

Mortality / viability:

not specified

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

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

not examined

Ophthalmological findings:

not specified

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Sexual maturation:

no effects observed

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Histopathological findings:

not specified

Other effects:

no effects observed

Behaviour (functional findings):

not examined

Developmental immunotoxicity:

not examined

Effects on F1 generation:The viability of the pups was not influenced by treatment. Development of pups from treated dams progressed in a similar manner to those pups from control dams i.e. no treatment related clinical signs were observed and body weight development was similat for treated and control litters. Macroscopic examination of the pups at necropsy did not detect any lesions that were associated with exposure of the parents to the test substance.

Key result

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

> 1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Remarks on result:

not determinable due to absence of adverse toxic effects

Key result

Reproductive effects observed:

no

Lowest effective dose / conc.:

1 000 mg/kg bw/day (actual dose received)

Treatment related:

no

Conclusions:

Based on the findings in the study, the no adverse effect level (NOAEL) for parental and developmental toxicity was established as more than 1000 mg/kg/day.

Executive summary:

Parental Data:

Adult males and females tolerated Hypersol Synergist L4722 at oral doses levels up to and including 1000 mg/kg/day without changes to appearance and behaviour, and without effect on survival, body weight or food intake.

There were no treatment-related macroscopic or microscopic lesions detected in parental animals.

Reproduction and litter data:

The result of the study indicate that mating was successful in all groups with similar mean coital times recorded for all groups. there was no indication of any treatment-related effects on fertility, since fertility and conception rates were similar for treated and control groups. Gestation times were unaffected by treatment.

The viability of the pups was not influenced by treatment. Development of pups from treated dams progressed in a similar manner to those pups from control dams i.e. no treatment-related clinical signs were observed and body weight development was similar for treated and control litters. Macroscopic examinations of the pups at necropsy did not detect any lesions that were associated with exposure of the parents to Hypersol Synergist L4722.

Based on the findings in the study, the no adverse effect level (NOAEL) for parental and developmental toxicity was established as more than 1000 mg/kg/day.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

reliable with restrictions

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Effects of test substance on fertility and developmental toxicity have been investigated in a One generation reproductive toxicity study (OECD 415). No treatment related effects were observed in parental animals or offspring up to the highest concentration tested (1000 mg/kg bw/day) indicating that the test substance do not affect fertility and offspring development.

Further toxicity data on the test substance support this interpretation:

- The test substance did not cause lethal effects after administration of a single oral dose of > 2000 mg/kg in rats,

- The test substance does not have to be classified as irritating to skin or eyes,

- it is unlikely that test substance become systemically bioavailable due to their extremely low solubility in water andn-octanoland due the missing bioavailability of the degradation product 3,3'-dichlorobenzidine after oral or dermal application.

Therefore it is concluded that the substances of this category will not cause effects on fertility and developmental toxicity and will not be transferred to breast milk.

Effects on developmental toxicity

Description of key information

Effects of test substance on fertility and developmental toxicity have been investigated in a One generation reproductive toxicity study (OECD 415). No treatment related effects were observed in parental animals or offspring up to the highest concentration tested (1000 mg/kg bw/day) indicating that the test substance do not affect fertility and offspring development.

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

other: Directive 87/302 , Part B OECD 414

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

Wistar

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 400

Details on exposure:

Method of administration or exposure: GavageMass median aerodynamic diameter:Not applicable

Frequency of treatment:

Dosing regime: 7 days/week

No. of animals per sex per dose:

Number of dams and doses24 at 0 mg/kg or mg/l24 at 50 mg/kg or mg/l24 at 200 mg/kg or mg/l24 at 1000 mg/kg or mg/l

Details on maternal toxic effects:

Details on maternal toxic effects:Treatment of pregnant females during day 6 to day 16 ofgestation inclusive, did not reveal any signs of maternaltoxocity.All mated females (except one) were pregnant and nodifferences were seen in the number of corpora lutea, thenumber of implantations, the pre- and post-implantation lossand the incidence of embryonic/foetal deaths.

Key result

Dose descriptor:

NOAEL

Effect level:

> 1 000 mg/kg bw/day

Basis for effect level:

other: maternal toxicity

Details on embryotoxic / teratogenic effects:

Details on embryotoxic / teratogenic effects:Effects on fetus - Gross:No foetal deaths occurred among treated litters. Sex ratios were normal in litters of dams treated with substance.The total foetal weights and foetal weights of the sexes separately revealed no test substance-related changes.
Effects on fetus -
Soft tissue: There were no external findings that were concidered to have arisen as a result of treatment of dams with the substance. There were no morphological changes detected at visceral examination of the foetuses.
Skeletal: Skeletal examinations revealed no changes in the ossification of the foetal skeleton at dose up to 1000 mg/kg body weight/day. Treatment of dams at 1000 mg/kg/day slightly increased the incidences of supernumerary ribs and wavy ribs.

Key result

Dose descriptor:

NOEL

Effect level:

200 mg/kg bw/day

Basis for effect level:

other: embryotoxicity

Key result

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no dose dependent effects except for slightly increased incidence of spontaneous variations at the highest dose.

Abnormalities:

effects observed, non-treatment-related

Localisation:

skeletal: supernumerary rib

Description (incidence and severity):

slight increase in incidence (frequent spontaneous variation)

Abnormalities:

effects observed, non-treatment-related

Localisation:

other: wavy rib

Description (incidence and severity):

silght increase in incidence (frequent spontaneous variation)

Developmental effects observed:

yes

Lowest effective dose / conc.:

1 000 mg/kg bw/day (nominal)

Treatment related:

no

Relation to maternal toxicity:

not specified

Dose response relationship:

no

Relevant for humans:

no

Conclusions:

Based on the results in this embryotoxicity and teratogenicy study, the definitive No Observed Effect Level (NOEL) was established as being 200 mg/kg bw/day. The NOAEL was considered as 1000 mg/kg bw/ day.

Executive summary:

Oral dosing of pregnant female Wistar rats with Hypersol synergist L 4722 at dose levels of 50, 200 or 1000 mg/kg bw/day during day 6 to 16 of gestation inclusive, was associated with a very slight increase in the total number of foetuses with supernumerary rib(s) or with wavy ribs, but there were no other indications of adverse effects upon in utero development of foetuses.

Based on the results in this embryotoxicity and teratogenicy study, the definitive No Observed Effect Level (NOEL) was established as being 200 mg/kg bw/day. The NOAEL was considered as 1000 mg/kg bw/ day.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

200 mg/kg bw/day

Additional information

Developmental toxicity / teratogenicity have been investigated in an Embryotoxicity and teratogenicity study with the test substance by oral gavage in Wistar Rats. The definitive No Obesrved Effect Level (NOEL) was established as being 200 kg/kg bw/day.

Justification for classification or non-classification

In the absence of any relevant local or systemic toxicity of the test substance after acute or repeated exposure and because they do not show any relevant bioavailability it is concluded that the test substance have not to be classified for reproductive toxicity and effects on or via lactation accordingto Regulation (EC) No 1272/2008 and Council Directive 67/548/EEC.