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The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Toxic effect type:
dose-dependent

Effects on fertility

Description of key information

Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test (OECD TG 422) – Oral Administration - The NOAEL for developmental toxicity was 1000 mg/kg/day and the NOAEL for reproductive toxicity was 1000 mg/kg/day.  

Additionally, an OECD 443 (extended one-generation reproductive toxicity - with developmental neurotoxicity (Cohorts 1A, 1B without extension, 2A and 2B)) test is proposed for structural analogues, Hydrocarbons, C9-C11, isoalkanes, cyclics, <2% aromatics and Hydrocarbons, C14-C19, isoalkanes, cyclics, <2% aromatics. This data is read across to based on analogue read across and a discussion and report on the read across strategy is provided as an attachment in IUCLID Section 13. 

This endpoint will be updated subsequent to ECHA's approval of the testing proposal and availability of data upon completion of the study. Additionally, an OECD Guideline 422 screening reproductive/developmental toxicity study (oral route) in rodents is planned with another structural analogue, Hydrocarbons, C9-C11, n-alkanes, isoalkanes, cyclics, <2% aromatics (EC# 919-857-5).

Link to relevant study records
Reference
Endpoint:
screening for reproductive / developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to or similar to guideline study OECD 422:GLP
Justification for type of information:
OECD Guideline 422 (Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
yes
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
not specified
Details on exposure:
Males were treated from day 14 prior to the mating phase until the end of the mating phase and then killed, Females were treated from day 14 prior to mating, through day 4 of lactation and then killed.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Males were dosed from the 14th day prior to mating, during mating until the end of the mating period. Females were dosed from the 14th day prior to the start of the mating phase to day 4 of lactation.
Frequency of treatment:
Single daily dose 7days/week
Remarks:
Doses / Concentrations:
0, 25, 150, or 1000 mg/kg/day (10 ml/kg dosing volume)
Basis:
other: gavage
No. of animals per sex per dose:
10 male, 10 female per group
Control group: 10 male, 10 female, 0.5% methylcellulose
Control animals:
yes
Parental animals: Observations and examinations:
Effects on general toxicity, neurobehavioral activity, clinical chemistry, and hematology were evaluated. Gross necropsies and histopathologic examination of tissues were conducted with emphasis on the male reproductive tract.
Reproductive assessment included mating, conception and fertility indices, reproductive organ weights and gross and histologic examination of the reproductive tract (special emphasis on stages of spermatogenesis in male gonads and interstitial testicular cell structure).
Sperm parameters (parental animals):
stages of spermatogenesis in male gonads and interstitial testicular cell structure
Litter observations:
Developmental toxicity assessment included, observations of external abnormalities, number of live and still births, mortality, sex determination and weights of pups.
Statistics:
Adult body weights and feed consumption, maternal body weight gains, gestation length and pup body weights were analyzed by ANOVA. Mean mating time was analyzed via the Kaplan Meier method. Pregnancy rates and mating, conception, viability index, post implantation losses, fertility and gestation indices were analyzed by the trend test, Chi-square 2XN and Fisher's exact test (all one tailed). The probability of survival per group was calculated by the product-limit procedure of Kaplan-Meier. Both a trend test and a log-rank test were used to analyze differences in survival among groups.
Clinical signs:
no effects observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Other effects:
not specified
Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed
No deaths or clinical signs of toxicity or behavioral changes were noted. No significant differences in body weights or feed consumption were observed. Startle reflex, open field test, and forelimb grip reflex performance data also revealed no treatment-related findings in the parental animals. There were also no treatment-related changes in hematology or blood chemistry parameters, organ weights or gross pathology. An apparent treatment-related, slight to moderate hyperplasia of the non-glandular mucosa of the stomach, associated with degeneration, hyperkeratosis and submucosal subacute inflammation and, in a few cases, with erosion, was seen in animals of all treated groups. This effect was considered an artifact of the dosing method and not directly related to the toxicity of the test material. No other treatment related histological changes were observed.

There were no treatment-related effects at any dose level on any of the reproductive parameters evaluated in this study. These included measures of reproductive performance (mating, conception, gestation length, litter size), offspring survival (gestation and postnatal survival indices, percent pre- and post-implantation loss). The mean mating time of the 1000 mg/kg/day groups was slightly longer than of the control, however, the increase was not statistically significant and within the normal range of variability for this strain of rats. There was a, non dose-related, decrease in fertility (decreased fertility index) was observed in all treated groups (not statistically significant) compared to controls. However, this effect took place in the absence of any adverse effects on reproductive organs and may have resulted from changes in mating behavior due related to stomach irritation experienced by the treated animals.
Key result
Dose descriptor:
NOAEL
Effect level:
>= 1 000 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
other: No effects noted at highest dose tested.
Clinical signs:
no effects observed
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Sexual maturation:
no effects observed
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Histopathological findings:
not specified
There were no treatment-related effects at any dose level on any of the reproductive parameters evaluated in this study including offspring survival (gestation and postnatal survival indices, percent pre- and post-implantation loss), pup body weight and pup sex ratio. There were also no treatment-related effects on any of the developmental parameters evaluated including external abnormalities, number of live and still births, mortality, sex determination and weights of pups.
Key result
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
>= 1 000 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
other: No effects noted at highest dose tested.
Reproductive effects observed:
not specified
Conclusions:
Oral dosing of Linpar 10 to male and female Sprague Dawley rats at levels of 0, 25, 150, or 1000 mg/kg body weight /day produced no evidence of developmental toxicity or teratogenicity and no statistically significant treatment-related effects on any of the reproductive parameters evaluated in this study. Based on these data, the no-observable-adverse effect level (NOAEL) for developmental toxicity was 1000 mg/kg/day and the NOAEL for reproductive toxicity was 1000 mg/kg/day, the highest dose tested.
Executive summary:

Groups of 10 male and 10 female Sprague Dawley rats were dosed with Linpar 10 daily by gavage at exposure levels of 0, 25, 150, or 1000 mg/kg/day Males were dosed from the 14th day prior to mating, during mating until the end of the mating period. Females were dosed from the 14th day prior to the start of the mating phase to day 4 of lactation.  There were no treatment-related effects at any dose level on any of the reproductive parameters evaluated in this study.  These included measures of reproductive performance (mating, conception, gestation length, litter size), offspring survival (gestation and postnatal survival indices, percent pre- and post-implantation loss), pup body weight and pup sex ratio. There were no treatment-related effects at any dose level on any of the developmental paramters evaluated in this study including external abnormalities of pups, number of live and still births, mortality, sex determination, and weights of pups.  Based on these data, the no-observable-adverse-effect level (NOAEL) for developmental toxicity was 1000 mg/kg/day and the NOAEL for reproductive toxicity was 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:
1 weight of evidence study is available.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

A decane OECD Guideline 422 study is available. Additionally, an OECD 443 (extended one-generation reproductive toxicity - with developmental neurotoxicity (Cohorts 1A, 1B without extension, 2A and 2B)) test is proposed for structural analogues, Hydrocarbons, C9-C11, isoalkanes, cyclics, <2% aromatics and Hydrocarbons, C14-C19, isoalkanes, cyclics, <2% aromatics. This data is read across to based on analogue read across and a discussion and report on the read across strategy is provided as an attachment in IUCLID Section 13. This endpoint will be updated subsequent to ECHA's approval of the testing proposal and availability of data upon completion of the study.

 

Oral

In an OECD Guideline 422 study (Sasol, 1995), groups of 10 male and 10 female Sprague Dawley rats were dosed with decane daily by gavage at exposure levels of 0, 25, 150, or 1000 mg/kg/day. Males were dosed from the 14th day prior to mating, during mating until the end of the mating period. Females were dosed from the 14th day prior to the start of the mating phase to day 4 of lactation. There were no treatment-related effects at any dose level on any of the reproductive parameters evaluated in this study. These included measures of reproductive performance (mating, conception, gestation length, litter size), offspring survival (gestation and postnatal survival indices, percent pre- and post-implantation loss), pup body weight and pup sex ratio. There were no treatment-related effects at any dose level on any of the developmental parameters evaluated in this study including external abnormalities of pups, number of live and still births, mortality, sex determination, and weights of pups. Based on these data, the no-observable-adverse-effect level (NOAEL) for developmental toxicity was 1000 mg/kg/day and the NOAEL for reproductive toxicity was 1000 mg/kg/day.

Effects on developmental toxicity

Description of key information

There is no data available for Decane. However, data is available for structural analogue Hydrocarbons, C9-C11, isoalkanes, cyclics, <2% aromatics. This data is read across to based on analogue read across and a discussion and report on the read across strategy is provided as an attachment in IUCLID Section 13. Additionally, OECD Guideline 414 (Prenatal Developmental Toxicity) rodent and non-rodent species tests are proposed for structural analogues, Hydrocarbons, C9-C11, isoalkanes, cyclics, <2% aromatics and Hydrocarbons, C14-C19, isoalkanes, cyclics, <2% aromatics. This endpoint will be updated subsequent to ECHA's approval of the testing proposals and availability of data upon completion of the studies.

Prenatal Developmental Toxicity Study (OECD TG 414) - Inhalation Administration - The maternal and developmental NOAECs were greater than 900 ppm (5220 mg/m3).

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable well-documented study report which meets basic scientific principles
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Principles of method if other than guideline:
Conducted according to the Food and Drug Administration 1966 "Guidelines for Reproduction Studies for Safety Evaluation of Drugs for Human Use", Segment II (Teratological Study)
GLP compliance:
no
Species:
rat
Strain:
Sprague-Dawley
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Bredding Laboratories
- Age at study initiation: females (58 days); males (sexually mature)

- Housing: individually except during mating
- Diet (e.g. ad libitum): ad libitum (food removed during exposure period)
- Water (e.g. ad libitum): ad libitum (water removed during exposure period)


Route of administration:
inhalation: vapour
Type of inhalation exposure (if applicable):
whole body
Details on exposure:
Appropriate amounts of test material were transferred from a reservoir using a metering pump into a heated flask and flash evaporated. A stream of clean air was also passed through the flask and the vapor laden air transferred to a port in the chamber air inlet, where it was diluted with normal chamber intake air to give the desired concentration. Adjustments in the exposure air concentration were made by changing the rate of the flow of test material through the metering pump.

The stainless steel and glass exposure chambers and an effective exposure volume of 760 liters. They were operated dynamically at a flow rate of approximately 125 liters per minute. This provided one air change every 8 minutes and a 99% equilibrium time of 39 minutes.

Atmospheric sampling was performed using a Wilks Scientific Corp Miran IA Ambient Air Analyzer (long pathlength infrared). The infrared spectrum of the test material was measured and a strong band associated with the test material was observed at 3.4 microns. Calibration curves relating the absorption at this wavelength to the airborne concentration of the test materials were prepared. On each exposure day, three samples were drawn from each exposure chamber and the exposure concentration calculated by comparing the absorption of this sample to the standard curve.

Postive control animals were treated via gastric intubation on gestational days 6-15 with 400mg/kg/day of acetylsalicylic acid in 0.5% methocel.
Analytical verification of doses or concentrations:
yes
Details on mating procedure:
All females selected for mating were places with male rats nightly in a 2:1 ratio. Vaginal smears were taken early in the morning and females were considered to have mated if sperm and/or a vaginal plug were observed. The day on which evidence of mating was first observed was established as Day 0 of gestation for that animal. Mated females were assigned to groups by daily body weight gain in an attempt to equalize Day 0 mean group body weights.
Duration of treatment / exposure:
Females were exposed on gestation days 6-15 by inhalation 6h/day
Frequency of treatment:
daily gestation days 6-15
Duration of test:
Day 6 of gestation ranged from 23 January-3 February 1978
Day 15 of gestation ranged for 1-12 February 1978
Remarks:
Doses / Concentrations:
300 ppm
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
900 ppm
Basis:
nominal conc.
No. of animals per sex per dose:
Negative control (Chamber air)- 20 mated females
Postive control (acetylsalicylic acid)-20 mated females
300 ppm- 21 mated females
900ppm- 21 mated females

Control animals:
yes, sham-exposed
other: positive control treated with 400mg/kg/day acetylsalicylic acid
Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily


BODY WEIGHT: Yes
- Time schedule for examinations: Days 0, 6-15, and 21 of gestation



POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 21
- Organs examined: uterus (number and location recorded for each horn of the following: live fetuses, dead fetuses, late resorptions, early resorptions, implantation sites); ovaries (number of corpora lutea per ovary)


Fetal examinations:
All fetuses were weighted, crown-rump distance measured, examined externally for malformations and sex determined externally (anogenital distance)
- External examinations: Yes: [all per litter ]
- Soft tissue examinations: Yes
- Skeletal examinations: Yes: [2/3 of litter ]
Fetuses designated for skeletal evaluation were eviscerated prior to initiation of the skeletal staining procedure. During the evisceration step the visceral contents of the thoracic and abdominal cavities were evaluated grossly in situ and sex was determined by internal inspection of gonads. Examination of skeleton for anomalies and ossification variations was performed after staining.
- Neural and Visceral defects: Yes: [1/3 of litter]
Statistics:
Comparisons between the negative control and treated groups and between the negative control and positive control groups were made where applicable by the chi-square method. Body weights, body weight gains, numbers of corpora lutea, implantations, resorptions, fetuses per dam, fetal and litter weights and crown-rump distances were compared to control by the F-test and Student’s t-test. When variances differed significantly, Student’s t-test was appropriately modified using Cochran’s approximation.
Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
Animals treated with 900 ppm exhibited a slight increase in excessive lacrimation during the treatment and post-treatment periods. This same group also exhibited an increased incidence of brown flakes in the fur covering the head area during the treatment period. Premature delivery of the litter on Day 21 of gestation prior to maternal sacrifice was observed in one negative control female, and two test material treated females. There were no remarkable gross postmortem changes in the treated adult females. All other physical observations occurred with similar frequencies in all groups and were considered to represent common observations noted in rats in the laboratory environment.

Positive control animals demonstrated statistically significant decreased body weight gain. Females had in utero litters containing fewer live fetuses and more resorption sites than untreated control litters. The implantation efficiency value was significantly reduced and the incidence of dams with two or more resorptions was increased.
Key result
Dose descriptor:
NOAEC
Effect level:
>= 5 220 mg/m³ air (nominal)
Basis for effect level:
other: maternal toxicity
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
All fetal survival, size and sex data for groups treated with test material were considered comparable to negative control data. Slight delays or variation in the normal ossification process were observed in treated animals. However such variation are common as the time of normal ossification can vary and were comparable to the variation observed in the control animals. The incidence of fetuses with external malformations and incidences of litters containing malformed fetuses in the groups treated with test material were considered comparable to the control data. No significant difference in the incidence of visceral malformations was observed in the treated groups. The incidence of fetuses with soft tissue malformation in groups treated with test material was comparable to the negative control.

In the positive control group, the percentage of live fetuses and mean fetal size data were significantly lower than the negative control and the percentage of resorbed fetuses was significantly higher than control. The incidence of fetuses with ossification variation was significantly higher than the control value. The incidence of fetuses with soft tissue malformations was significantly higher in the positive control treated group than the negative control.
Key result
Dose descriptor:
NOAEC
Effect level:
>= 5 220 mg/m³ air (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Developmental Toxicity
Abnormalities:
not specified
Developmental effects observed:
no
Conclusions:
There was no evidence of maternal or fetal toxicity at either exposure level of MRD-77-44 tested. Based on these results, both the maternal and developmental NOAELs were greater than or equal to 900 ppm (>= 5220 mg/m^3).
Executive summary:

MRD-77-44 was administered to pregnant female rats by inhalation exposure to vapor concentrations of 300 or 900 ppm, 6 hours/day during gestation days 6 to 15 to assess developmental toxicity.  Included in this study was a negative control (chamber exposed) group and a positive control group that was treated via gastric intubation on gestational days 6-15 with 400mg/kg/day of acetylsalicylic acid.  All surviving females were sacrificed on Day 21 of testation and fetuses examined for external, soft tissue and skeletal malformations.  Pregnancy rate, mortality, body weight gain and gross postmortem observations were unaffected by treatment.  MRD-77-44 treatment at either dose level had no effect on reproductive endpoints, fetal size, sex distribution, ossification variation, or fetal examination endpoints.    Thus, there was no evidence of maternal or fetal toxicity at either exposure level of MRD-77-44 tested.  Based on these results, both the maternal and developmental NOAELs were greater than or equal to 900 ppm (5220 mg/m3).

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
5 220 mg/m³
Study duration:
subacute
Species:
rat
Quality of whole database:
1 weight of evidence study available from a structural analogue.
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

There is no data available for Decane. However, data is available for structural analogue Hydrocarbons, C9-C11, isoalkanes, cyclics, <2% aromatics. This data is read across to based on analogue read across and a discussion and report on the read across strategy is provided as an attachment in IUCLID Section 13.

Inhalation

In an OECD TG 414 study (ExxonMobil, 1978) the test material (Hydrocarbons, C9-C11, isoalkanes, cyclics, <2% aromatics) was administered to pregnant female rats by inhalation exposure to vapor concentrations of 300 or 900 ppm, 6 hours/day during gestation days 6 to 15 to assess developmental toxicity.  Included in this study was a negative control (chamber exposed) group and a positive control group that was treated via gastric intubation on gestational days 6-15 with 400mg/kg/day of acetylsalicylic acid.  All surviving females were sacrificed on Day 21 of testing and fetuses examined for external, soft tissue and skeletal malformations.  Pregnancy rate, mortality, body weight gain and gross postmortem observations were unaffected by treatment.  Hydrocarbons, C9-C11, isoalkanes, cyclics, <2% aromatics treatment at either dose level had no effect on reproductive endpoints, fetal size, sex distribution, ossification variation, or fetal examination endpoints.    Thus, there was no evidence of maternal or fetal toxicity at either exposure level of Hydrocarbons, C9-C11, isoalkanes, cyclics, <2% aromatics tested.  Based on these results, both the maternal and developmental NOAECs were greater than or equal to 900 ppm (5220 mg/m3).

Additionally, OECD Guideline 414 (Prenatal Developmental Toxicity) rodent and non-rodent species tests are proposed for structural analogues, Hydrocarbons, C9-C11, isoalkanes, cyclics, <2% aromatics and Hydrocarbons, C14-C19, isoalkanes, cyclics, <2% aromatics. This endpoint will be updated subsequent to ECHA's approval of the testing proposals and availability of data upon completion of the studies.

Justification for classification or non-classification

Based on the data available and available read across data from structural analogues, Decane does not warrant classification as a reproductive or developmental toxicant under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

However, an OECD 422 test will be conducted on a structural analogue Hydrocarbons, C9-C11, n-alkanes, isoalkanes, cyclics, <2% aromatics (EC# 919-857-5). Additional tests (OECD 443 and OECD 414 (rodent and 2nd species)) are proposed and will be conducted subsequent to ECHA's approval of the same. This endpoint will be updated upon completion of the above studies subject to ECHA's approval.

Additional information