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EC number: 919-164-8 | CAS number: -
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Description of key information
No reproductive toxicity/fertility data is available for Hydrocarbons, C10-C13, n-alkanes, isoalkanes, cyclics, aromatics (2-25%). However, data is available for structural analogue, Hydrocarbons, C9-C12, n-alkanes, isoalkanes, cyclics, aromatics (2-25%). 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.
Hydrocarbons, C9-C12, n-alkanes, isoalkanes, cyclics, aromatics (2-25%):
NOAEC for reproductive toxicity in rats ≥ 300 ppm (1720 mg/m3)
Additionally, an OECD 443 test is proposed for Hydrocarbons, C10-C13, n-alkanes, isoalkanes, cyclics, aromatics (2-25%). This endpoint will be updated subsequent to ECHA's approval of the testing proposal and availability of data upon completion of the study.
Link to relevant study records
- Endpoint:
- screening for reproductive / developmental toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- supporting study
- Study period:
- 1980
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study.
- Justification for type of information:
- The justification for read across is provided 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 421 (Reproduction / Developmental Toxicity Screening Test)
- GLP compliance:
- no
- Limit test:
- yes
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, MA
- Age at study initiation: males - 10 weeks, females - 9 weeks at initiation of pre-treatment mating period, 8 weeks at initiation of post-treatment mating period
- Weight at study initiation: 281-289 g
- Housing: stainless steel wire mesh cages, animals were housed individually during exposure and at a 2:1 female/male ratio during mating
- Diet (e.g. ad libitum): Purina Laboratory Chow, ad libitum
- Water (e.g. ad libitum): ad libitum
IN-LIFE DATES: From: August 21, 1978 To Oct. 13, 1978 - Route of administration:
- inhalation: vapour
- Type of inhalation exposure (if applicable):
- whole body
- Details on exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: one cubic meter stainless steel and glass chamber
- Method of conditioning air: The MRD-78-25 (300 ppm) was transferred from a 500 ml Erlenmeyer flask using a metering pump, or a 50 cc Tomac glass syringe into a heated flask (100 ppm) and flash evaporated. Clean air was also passed through the flask to pick up vapor. The vapor air mixture was then fed into the chamber inlets and diluted to the desired concentration. The MRD-78-26 was put in fritted bottom gas-washing bottles (400 and 1200 ppm). Air was passed through the bottles, and the vapor air mixture was then fed into the chamber inlets and diluted to the desired concentration.
- Air flow rate: 132 l/min
- Air change rate: complete air change every 7.6 min, with a 99% equilibration time of 35 min. - Details on mating procedure:
- Each male cohabitated for two weeks with two females. Females were sacrificed 18 days after beginning cohabitation. Males were then exposed to the test substance for 8 weeks. Two hours after the last exposure, two untreated virgin females were placed in the males cages. These females cohabitated for seven days and replaced with two new females.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- - Brief description of analytical method used: IR spectrum taken with a Miran IA Ambient Air Analyzer (Wilks Scientific Corp.), analyzed at 3.4 microns.
- Samples taken from breathing zone: yes, at 1, 3, and 5 hrs after exposure began each day - Duration of treatment / exposure:
- 6 hours/day
- Frequency of treatment:
- 5 days/week for 8 weeks
- Remarks:
- Doses / Concentrations:
100 ppm
Basis:
nominal conc. - Remarks:
- Doses / Concentrations:
300 ppm
Basis:
nominal conc. - No. of animals per sex per dose:
- 10 males, 40 females
- Control animals:
- yes, concurrent no treatment
- Positive control:
- triethylenemelamine
- Justification for choice of positive control(s): Triethylenemelamine has been shown to induce dominant-lethal mutations
- Route of administration: intraperitoneally
- Doses / concentrations: 0.5 mg/kg - Parental animals: Observations and examinations:
- Animals were examined for mortality, pharmacological observations, toxicological observations (twice daily), physical observations, body weight (weekly), gross necropsy, and histopathology (seminal vesicles, epididymis, testes, prostate).
- Postmortem examinations (parental animals):
- The following organs were examined in males: seminal vesicles, epididymis, testes, prostate.
- Statistics:
- Comparisons between controls and treatment groups were made using the Chi-square method. Data was compared using the F-test and student's t-test, with the student's t-test modified using Cochran's approximation.
- Reproductive indices:
- Males were considered fertile if at least one female became pregnant.
- Offspring viability indices:
- implantation sites, early resorption sites, late resorption sites, viable fetal swellings
- 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 examined
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- >= 300 ppm
- Sex:
- male/female
- Basis for effect level:
- other: 1720 mg/m3
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not examined
- Key result
- Dose descriptor:
- NOAEC
- Generation:
- F1
- Effect level:
- >= 300 ppm
- Sex:
- male/female
- Basis for effect level:
- other: 1720 mg/m3
- Reproductive effects observed:
- not specified
- Conclusions:
- The NOAEC for reproductive and developmental screening is 300 ppm in rats via inhalation.
- Executive summary:
This study was conducted to assess the reproductive and developmental toxicity potential of MRD-78-25 when administered to male rats. Male rats were cohabitated for two weeks with two female rats. Males were exposed for 6 hrs/day, 5 days/week, for 8 weeks. At the end of the 8 week exposure period, the male rats the cohabitated for 7 days with two virgin female rats. After this cohabitation, the males were again cohabitated with two new virgin females for another 7 days. 18 days after the beginning of cohabitation, the females were sacrificed. There were also a negative control group, and a positive control group exposed to triethylenemelamine prior to mating. Animals were examined for mortality, pharmacological observations, toxicological observations, physical observations, body weight, gross necropsy, and histopathology. Males proven fertile were then exposed to 100 or 300 ppm of test substance vapors via inhalation (10 males per concentration). The number of implantation sites, early resorption sites, late resorption sites, and viable fetal swellings were also examined. Pregnancy rates, implantation rate, and implantation efficiency were comparable between exposure groups and negative controls. The NOAEC for reproductive screening is 300 ppm for rats via inhalation.
- Endpoint:
- extended one-generation reproductive toxicity - with developmental neurotoxicity (Cohorts 1A, 1B without extension, 2A and 2B)
- Type of information:
- experimental study planned
- Study period:
- Will be completed in the timescale as indicated in the ECHA decision letter.
- Justification for type of information:
- This testing proposal has been presented in the lead registrant dossier for this substance submitted to ECHA in 2019. This is a source dossier where the overall approach should be seen in the context of a category of 108 different substances, where the substances are hydrocarbon solvents covering a carbon number range of C5-C20, based on alkane constituents and a range from approximately C8-C18 for aromatic constituents. The basis for this test proposal is set out in detail in the document ‘Hydrocarbon Solvents Test Proposals, Test Plans and Read-Across Strategy for Human Health Endpoints’, which is attached to this endpoint study record and in Section 13.2 of the IUCLID dossier.
TESTING PROPOSAL ON VERTEBRATE ANIMALS
NON-CONFIDENTIAL NAME OF SUBSTANCE:
- Name of the substance on which testing is proposed to be carried out : Hydrocarbons, C10-C13, n-alkanes, isoalkanes, cyclics, aromatics (2-25%) (EC# 919-164-8)
- Name of the substance for which the testing proposal will be used [if different from tested substance] : Not different
CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION [please address all points below]:
- Available GLP studies : There are no OECD Guideline 443 studies available on this substance to evaluate the reproductive toxicity endpoint.
- Available non-GLP studies : There are no ‘non-GLP’ studies available for this substance to evaluate the reproductive toxicity endpoint.
- Historical human data: No human data exist for this substance to evaluate reproductive toxicity hazard.
- (Q)SAR : There are no recognised (Q)SAR methods available for reliable prediction of reproductive toxicity.
- In vitro methods : There are no in vitro methods currently accepted by Regulatory Authorities for the reliable prediction of reproductive toxicity.
- Weight of evidence : Currently there are insufficient data available to develop a robust weight of evidence approach for reproductive toxicity.
- Grouping and read-across : This test proposal maybe used to help develop a category approach for a wider range of hydrocarbons.
- Substance-tailored exposure driven testing [if applicable] : Insufficient data available
- Approaches in addition to above [if applicable]: None applicable
- Other reasons [if applicable] : None identified
CONSIDERATIONS THAT THE SPECIFIC ADAPTATION POSSIBILITIES OF ANNEXES VI TO X (AND COLUMN 2 THEREOF) OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
- There are no specific adaptions for this endpoint
FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
- Details on study design / methodology proposed: See 'any other information on materials and methods incl. tables' for further information. - Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 443 (Extended One-Generation Reproductive Toxicity Study)
- GLP compliance:
- yes (incl. QA statement)
- Justification for study design:
- SPECIFICATION OF STUDY DESIGN FOR EXTENDED ONE-GENERATION REPRODUCTION TOXICITY STUDY WITH JUSTIFICATIONS:
See 'any other information on materials and methods incl. tables' for further information. - Species:
- rat
- Sex:
- male/female
- Route of administration:
- oral: feed
Referenceopen allclose all
Mean Body Weights (g)
Week |
Negative Control |
Positive Control |
100 ppm |
300 ppm |
Initial |
289 |
281 |
283 |
284 |
Pre-treatment mating 1 |
331 |
325 |
328 |
328 |
Pre-treatment mating 2 |
365 |
362 |
367 |
363 |
Treatment 1 |
413 |
418 |
416 |
407 |
Treatment 2 |
438 |
449 |
441 |
428 |
Treatment 3 |
452 |
470 |
458 |
443 |
Treatment 4 |
470 |
487 |
475 |
459 |
Treatment 5 |
480 |
504 |
490 |
470 |
Treatment 6 |
484 |
516 |
502 |
479 |
Treatment 7 |
496 |
531 |
518 |
487 |
Treatment 8 |
504 |
538 |
527 |
500 |
Post-treatment mating 1 |
514 |
508 |
535 |
507 |
Post-treatment mating 2 |
523 |
518 |
544 |
516 |
Reproduction Data
Pregnancy Rate (%) |
||||
Week |
Negative Control |
Positive Control |
100 ppm |
300 ppm |
Pre-treatment mating 1 |
75.0 |
70.0 |
70.0 |
70.0 |
Pre-treatment mating 2 |
80.0 |
85.0 |
90.0 |
95.0 |
Post-treatment mating 1 |
85.0 |
75.0 |
80.0 |
65.0 |
Post-treatment mating 2 |
100.0 |
80.0 |
95.0 |
100.0 |
Mean Corpora Lutea |
||||
Pre-treatment mating 1 |
12.5 |
11.8 |
12.9 |
14.0 |
Pre-treatment mating 2 |
14.1 |
14.9 |
13.1 |
13.5 |
Post-treatment mating 1 |
13.1 |
11.1 |
13.9 |
13.4 |
Post-treatment mating 2 |
13.4 |
11.9 |
14.4 |
13.1 |
Mean Implantations |
||||
Pre-treatment mating 1 |
10.1 |
11.4 |
12.0 |
13.0 |
Pre-treatment mating 2 |
12.5 |
14.0 |
12.1 |
11.9 |
Post-treatment mating 1 |
11.9 |
8.8 |
12.6 |
12.6 |
Post-treatment mating 2 |
12.7 |
4.1 |
12.8 |
12.5 |
Implantation Efficiency |
||||
Pre-treatment mating 1 |
80.9 |
96.4 |
92.8 |
92.9 |
Pre-treatment mating 2 |
88.5 |
94.1 |
92.3 |
88.3 |
Post-treatment mating 1 |
91.0 |
79.0 |
91.0 |
94.3 |
Post-treatment mating 2 |
95.1 |
34.0 |
89.4 |
95.4 |
Mean Early Fetal Death |
||||
Pre-treatment mating 1 |
0.2 |
0.4 |
0.6 |
0.5 |
Pre-treatment mating 2 |
0.6 |
0.5 |
0.5 |
1.0 |
Post-treatment mating 1 |
0.8 |
5.9 |
0.5 |
0.8 |
Post-treatment mating 2 |
0.5 |
4.1 |
0.9 |
0.5 |
Mean Late Fetal Death |
||||
Pre-treatment mating 1 |
0.1 |
0.0 |
0.0 |
0.0 |
Pre-treatment mating 2 |
0.0 |
0.0 |
0.0 |
0.1 |
Post-treatment mating 1 |
0.0 |
0.1 |
0.0 |
0.0 |
Post-treatment mating 2 |
0.0 |
0.0 |
0.0 |
0.0 |
Viable Fetal Swellings |
||||
Pre-treatment mating 1 |
9.9 |
10.9 |
11.4 |
12.5 |
Pre-treatment mating 2 |
11.9 |
13.5 |
11.6 |
10.8 |
Post-treatment mating 1 |
11.1 |
2.8 |
12.1 |
11.8 |
Post-treatment mating 2 |
12.2 |
0.0 |
11.9 |
12.1 |
Effect on fertility: via oral route
- Endpoint conclusion:
- no study available
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEC
- 1 720 mg/m³
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- 1 key read across study from a structural analogue available for assessment
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
No reproductive toxicity/fertility data is available for Hydrocarbons, C10-C13, n-alkanes, isoalkanes, cyclics, aromatics (2-25%). However, data is available for structural analogue, Hydrocarbons, C9-C12, n-alkanes, isoalkanes, cyclics, aromatics (2-25%). 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.
Hydrocarbons, C9-C12, n-alkanes, isoalkanes, cyclics, aromatics (2-25%)
A read across OECD Guideline 421 screening reproductive toxicity study (ExxonMobil, 1980a), was conducted to assess the reproductive and developmental toxicity potential of the test material (Hydrocarbons, C9-C12, n-alkanes, isoalkanes, cyclics, aromatics (2-25%)) when administered to male rats. Male rats were cohabitated for two weeks with two female rats. Males were exposed for 6 hrs/day, 5 days/week, for 8 weeks. At the end of the 8 week exposure period, the male rats the cohabitated for 7 days with two virgin female rats. After this cohabitation, the males were again cohabitated with two new virgin females for another 7 days. 18 days after the beginning of cohabitation, the females were sacrificed. There were also a negative control group, and a positive control group exposed to triethylenemelamine prior to mating. Animals were examined for mortality, pharmacological observations, toxicological observations, physical observations, body weight, gross necropsy, and histopathology. Males proven fertile were then exposed to 100 or 300 ppm of test substance vapors via inhalation (10 males per concentration). The number of implantation sites, early resorption sites, late resorption sites, and viable fetal swellings were also examined. Pregnancy rates, implantation rate, and implantation efficiency were comparable between exposure groups and negative controls. The NOAEC for reproductive screening was determined to be ≥300 ppm for rats via inhalation.
Additionally, an OECD 443 test is proposed for Hydrocarbons, C10-C13, n-alkanes, isoalkanes, cyclics, aromatics (2-25%). This endpoint will be updated subsequent to ECHA's approval of the testing proposal and availability of data upon completion of the study.
Effects on developmental toxicity
Description of key information
No developmental toxicity data is available for Hydrocarbons, C10-C13, n-alkanes, isoalkanes, cyclics, aromatics (2-25%). However, data is available for structural analogue, Hydrocarbons, C9-C12, n-alkanes, isoalkanes, cyclics, aromatics (2-25%). 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.
Hydrocarbons, C9-C12, n-alkanes, isoalkanes, cyclics, aromatics (2-25%)
NOAEC for developmental toxicity: ≥ 300 ppm (1575 mg/m3)
Additionally, OECD Guideline 414 rodent and non-rodent species tests are proposed for Hydrocarbons, C10-C13, n-alkanes, isoalkanes, cyclics, aromatics (2-25%). This endpoint will be updated subsequent to ECHA's approval of the testing proposals and availability of data upon completion of the studies.
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 11 Sept. 1978 - 6 Oct. 1978
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study.
- Justification for type of information:
- The justification for read across is provided as an attachment in IUCLID Section 13.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- according to guideline
- Guideline:
- other: Guidelines for Reproduction Studies for Safety and Evaluation of Drugs for Human Use, Segment II (Teratology Study)
- GLP compliance:
- no
- Limit test:
- yes
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc.
- Age at study initiation: 7 weeks
- Fasting period before study: Animals were not given food during exposure.
- Housing: Individually, except during mating, in stainless steel cages, animals identified by ear tags
- Diet (e.g. ad libitum): Purina Lab Chow, ad libitum
- Water (e.g. ad libitum): Elizabethtown Water Company, ad libitum
- Acclimation period: Aug. 17, 1978-Sept. 4, 1978
ENVIRONMENTAL CONDITIONS
- Temperature (°C): monitored twice daily, room temperature
- Humidity (%): dry air
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark
IN-LIFE DATES: days 6-15 of gestation From: 11-27 Sept. 1978 To: 20 Sept. - 6 Oct. 1978 - Route of administration:
- inhalation: vapour
- Type of inhalation exposure (if applicable):
- whole body
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: one cubic meter exposure chamber
- Temperature, humidity, pressure in air chamber: room temperature, dry air - Analytical verification of doses or concentrations:
- no
- Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1/1
- Length of cohabitation: Overnight and removed in morning to check for pregnancy, this was repeated until females were pregnant
- Proof of pregnancy: vaginal plug and sperm in vaginal smear referred to as day 0 of pregnancy - Duration of treatment / exposure:
- 6 hrs/day
- Frequency of treatment:
- days 6-15 of gestation
- Duration of test:
- days 6-15 of gestation
- No. of animals per sex per dose:
- 20
- Control animals:
- yes, concurrent no treatment
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
- Cage side observations: mortality, toxicological signs, pharmacological effects
BODY WEIGHT: Yes
- Time schedule for examinations: days 0, 6-15, 21 of gestation
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day #: 21
- Organs examined: uterus, ovaries - Ovaries and uterine content:
- The ovaries and uterine content were examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other: number of live fetuses, number of dead fetuses - Fetal examinations:
- - External examinations: Yes: all per litter examined for sex, crown-rump distance, weighed, and malformations
- Soft tissue examinations: Yes: 2/3 per litter examined for gross dissection and examination of viscera, internal sex determination, ureter, kidneys, and heart
- Skeletal examinations: Yes: 2/3 per litter examined for skeletal malformations, and ossification
- Head examinations: Yes: 1/3 per litter examined for neural defects - Statistics:
- Analysis was done using the chi-square method, or the F-test and Student's t-test. When the variance differed significantly, the Student's t-test was modified suing Chochran's approximation. The mean number of live fetuses, resorptions, implantations, and corpora lutea were analyzed using the one-tailed t-test.
- Indices:
- implantation efficiency,
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
Details on maternal toxic effects:
There was no mortality in either of the dosage groups. Pregnancy rates were comparable between the exposure groups and negative controls. Weight gain was significantly higher in the exposure groups post-dosing. There were no significant clinical observations in either exposure group. The mean number of corpora lutea was significantly decreased in the 300 ppm group. Since ovulation occurred prior to exposure, this was not considered to be treatment related. The mean number of implantations was comparable between exposure groups and negative controls. The implantation efficiency values were actually significantly higher in exposure groups as compared to negative controls. The mean number of live fetuses, resorption sites, and number of dams with more than one resorption site were comparable between exposures and negative controls. The gross postmortem examination of dams showed no treatment related effects. - Key result
- Dose descriptor:
- NOAEC
- Effect level:
- >= 300 ppm
- Basis for effect level:
- other: Systemic toxicity
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
The body weights of fetal males in the 100 ppm group were significantly higher than negative controls. There were some statistically significant differences in mean crown-rump distance between both dosage levels and negative controls, these differences were slight and the effect inconsistant between dosages and sex. These differences were therefore not considered to be indicative of a treatment related effect. Mean numbers of male and female fetuses, and sex ratios were similar between exposure groups and negative controls. Ossification variations were similar in exposure groups and negative controls, as was the incidence of litters with fetuses containing ossification variations. No malformations externally or in the soft tissues were noted in the fetuses except in the positive controls. Though skeletal defects were noted in the exposure group, the types of malformations are common in rat fetus and not considered to be treatment related. - Key result
- Dose descriptor:
- NOAEC
- Effect level:
- >= 300 ppm
- Based on:
- test mat.
- Basis for effect level:
- other: Developmental Toxicity
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- The NOAEC for developmental toxicity in rats is >=300 ppm (1575 mg/m3) via inhalation. The test substance is also non-teratogenic.
- Executive summary:
This study determined the developmental toxicity of MRD-78 -25 in rats exposed via inhalation. Groups of 20 pregnant female rats were exposed 6 hrs/day during days 6 -15 of gestation. Test concentrations of 100 or 300 ppm test substance. In addition to a negative control group, there was also a positive control group that was exposed to acetylsalicylic acid on days 6 -15 of gestation. Dams were observed for toxicological signs and pharmacological effects. On day 21 of gestation, the animals were sacrificed, and examined for corpora lutea and uterine implantation parameters. Fetuses were examined for fetal size, sex ratio, and external, soft-tissue, and skeletal malformations. No adverse effects due to exposure to the test substance were seen in either dams or fetuses. No treatment related malformation effects were noted in the fetuses. The developmental NOAEC for rats by inhalation is >=300 ppm. The test substance is also not teratogenic.
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study planned
- Study period:
- Will be completed in the timescale as indicated in the ECHA decision letter.
- Justification for type of information:
- This testing proposal has been presented in the lead registrant dossier for this substance submitted to ECHA in 2019. This is a source dossier where the overall approach should be seen in the context of a category of 108 different substances, where the substances are hydrocarbon solvents covering a carbon number range of C5-C20, based on alkane constituents and a range from approximately C8-C18 for aromatic constituents. The basis for this test proposal is set out in detail in the document ‘Hydrocarbon Solvents Test Proposals, Test Plans and Read-Across Strategy for Human Health Endpoints’, which is attached to this endpoint study record and in Section 13.2 of the IUCLID dossier.
TESTING PROPOSAL ON VERTEBRATE ANIMALS
[Please provide information for all of the points below. The information should be specific to the endpoint for which testing is proposed. Note that for testing proposals addressing testing on vertebrate animals under the REACH Regulation this document will be published on the ECHA website along with the third party consultation on the testing proposal(s).]
NON-CONFIDENTIAL NAME OF SUBSTANCE:
- Name of the substance on which testing is proposed to be carried out : Hydrocarbons, C10-C13, n-alkanes, isoalkanes, cyclics, aromatics (2-25%) (EC# 919-164-8)
- Name of the substance for which the testing proposal will be used [if different from tested substance] : Not different
CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION [please address all points below]:
- Available GLP studies : There are no OECD Guideline 414 studies available on this substance to evaluate the developmental toxicity endpoint in both rodents and non-rodents.
- Available non-GLP studies : There are no ‘non-GLP’ studies available for this substance to evaluate the developmental toxicity endpoint in both rodent and non-rodent species.
- Historical human data : - No human data exist for this substance to evaluate developmental toxicity hazard.
- (Q)SAR : There are no recognised (Q)SAR methods available for reliable prediction of developmental toxicity.
- In vitro methods : There are no in vitro methods currently accepted by Regulatory Authorities for the reliable prediction of developmental toxicity.
- Weight of evidence : Currently there are insufficient data available to develop a robust weight of evidence approach for developmental toxicity.
- Grouping and read-across : This test proposal maybe used to help develop a category approach for a wider range of hydrocarbons.
- Substance-tailored exposure driven testing [if applicable] : Insufficient data available
- Approaches in addition to above [if applicable]: None applicable
- Other reasons [if applicable] : None identified
CONSIDERATIONS THAT THE SPECIFIC ADAPTATION POSSIBILITIES OF ANNEXES VI TO X (AND COLUMN 2 THEREOF) OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
- As the registration dossier is submitted above 1000 tonnes, studies in both species will be conducted.
FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
- Details on study design / methodology proposed [if relevant]: See 'Materials and Methods' Section for further information. - Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- yes (incl. QA statement)
- Species:
- rat
- Route of administration:
- oral: unspecified
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study planned
- Study period:
- Will be completed in the timescale as indicated in the ECHA decision letter.
- Justification for type of information:
- This testing proposal has been presented in the lead registrant dossier for this substance submitted to ECHA in 2019. This is a source dossier where the overall approach should be seen in the context of a category of 108 different substances, where the substances are hydrocarbon solvents covering a carbon number range of C5-C20, based on alkane constituents and a range from approximately C8-C18 for aromatic constituents. The basis for this test proposal is set out in detail in the document ‘Hydrocarbon Solvents Test Proposals, Test Plans and Read-Across Strategy for Human Health Endpoints’, which is attached to this endpoint study record and in Section 13.2 of the IUCLID dossier.
TESTING PROPOSAL ON VERTEBRATE ANIMALS
[Please provide information for all of the points below. The information should be specific to the endpoint for which testing is proposed. Note that for testing proposals addressing testing on vertebrate animals under the REACH Regulation this document will be published on the ECHA website along with the third party consultation on the testing proposal(s).]
NON-CONFIDENTIAL NAME OF SUBSTANCE:
- Name of the substance on which testing is proposed to be carried out : Hydrocarbons, C10-C13, n-alkanes, isoalkanes, cyclics, aromatics (2-25%) (EC# 919-164-8)
- Name of the substance for which the testing proposal will be used [if different from tested substance] : Not different
CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION [please address all points below]:
- Available GLP studies : There are no OECD Guideline 414 studies available on this substance to evaluate the developmental toxicity endpoint in both rodents and non-rodents.
- Available non-GLP studies : There are no ‘non-GLP’ studies available for this substance to evaluate the developmental toxicity endpoint in both rodent and non-rodent species.
- Historical human data : - No human data exist for this substance to evaluate developmental toxicity hazard.
- (Q)SAR : There are no recognised (Q)SAR methods available for reliable prediction of developmental toxicity.
- In vitro methods : There are no in vitro methods currently accepted by Regulatory Authorities for the reliable prediction of developmental toxicity.
- Weight of evidence : Currently there are insufficient data available to develop a robust weight of evidence approach for developmental toxicity.
- Grouping and read-across : This test proposal maybe used to help develop a category approach for a wider range of hydrocarbons.
- Substance-tailored exposure driven testing [if applicable] : Insufficient data available
- Approaches in addition to above [if applicable]: None applicable
- Other reasons [if applicable] : None identified
CONSIDERATIONS THAT THE SPECIFIC ADAPTATION POSSIBILITIES OF ANNEXES VI TO X (AND COLUMN 2 THEREOF) OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
- As the registration dossier is submitted above 1000 tonnes, studies in both species will be conducted.
FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
- Details on study design / methodology proposed [if relevant] - Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- yes (incl. QA statement)
- Species:
- rabbit
- Route of administration:
- oral: unspecified
Referenceopen allclose all
Results - Dams
Endpoint |
Negative Control |
400 mg/kg ASA |
100 ppm |
300 ppm |
Pregnancy Rate (%) |
100.0 |
95.0 |
100.0 |
90.0 |
Mortality Rate (%) |
0.0 |
10.0 |
0.0 |
0.0 |
Mean Body Weight Gain (g) Dams - Days 15-21 |
84 |
32 |
108 |
103 |
Mean Corpora Lutea |
15.2 |
14.5 |
15.5 |
13.8 |
Mean No. Implantations |
13.0 |
13.2 |
13.8 |
13.2 |
Implantation Efficiency (%) |
85.8 |
91.1 |
88.7 |
95.6 |
Mean No. Live Fetuses |
12.5 |
7.4 |
12.9 |
12.6 |
Mean No. Dead Fetuses |
0.0 |
0.0 |
0.0 |
0.0 |
Mean No. Resorptions |
0.6 |
5.8 |
0.9 |
0.7 |
Dams with more than one Resorption (%) |
10.0 |
58.8 |
25.0 |
11.1 |
Results – Fetuses
Endpoint |
Negative Control |
400 mg/kg ASA |
100 ppm |
300 ppm |
Male Mean Fetal Weight (g) |
5.57 |
3.88 |
5.82 |
5.62 |
Female Mean Fetal Weight (g) |
5.29 |
3.62 |
5.44 |
5.33 |
Male Mean Crown-Rump Distance (cm) |
4.3 |
3.7 |
4.4 |
4.2 |
Female Mean Crown-Rump Distance (cm) |
4.2 |
3.6 |
4.2 |
4.1 |
Sex Ratio (%) |
91.5 |
98.4 |
88.3 |
105.5 |
Ossification Variations (%) |
70.7 |
100.0 |
79.4 |
79.3 |
Litters with Ossification Variations (%) |
100.0 |
100.0 |
95.0 |
100.0 |
Soft Tissue Malformations (%) |
2.4 |
26.8 |
1.1 |
3.9 |
Litters with Soft Tissue Malformations (%) |
10.0 |
54.5 |
5.0 |
16.7 |
Gross Evisceration Malformations (%) |
5.4 |
3.6 |
1.8 |
4.0 |
Litters with Gross Evisceration Malformations |
25.0 |
8.3 |
10.0 |
16.7 |
Skeletal Malformations (%) |
0.0 |
21.4 |
2.9 |
1.3 |
Litters with Skeletal Malformations |
0.0 |
66.7 |
15.0 |
11.1 |
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
- 1 575 mg/m³
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- 1 key read-across study from a structural analogue available for assessment
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Additional information
No developmental toxicity data is available for Hydrocarbons, C10-C13, n-alkanes, isoalkanes, cyclics, aromatics (2-25%). However, data is available for structural analogue, Hydrocarbons, C9-C12, n-alkanes, isoalkanes, cyclics, aromatics (2-25%). 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.
Hydrocarbons, C9-C12, n-alkanes, isoalkanes, cyclics, aromatics (2-25%)
A key study (ExxonMobil, 1979b) determined the developmental toxicity of the test material (Hydrocarbons, C9-C12, n-alkanes, isoalkanes, cyclics, aromatics (2-25%)) in rats exposed via inhalation. Groups of 20 pregnant female rats were exposed 6 hrs/day during days 6 -15 of gestation. Test concentrations of 100 or 300 ppm test substance. In addition to a negative control group, there was also a positive control group that was exposed to acetylsalicylic acid on days 6 -15 of gestation. Dams were observed for toxicological signs and pharmacological effects. On day 21 of gestation, the animals were sacrificed, and examined for corpora lutea and uterine implantation parameters. Fetuses were examined for fetal size, sex ratio, and external, soft-tissue, and skeletal malformations. No adverse effects due to exposure to the test substance were seen in either dams or fetuses. No treatment related malformation effects were noted in the fetuses. The developmental NOAEC for rats by inhalation was determined to be >=300 ppm. The test substance is also not teratogenic.
Additionally, OECD Guideline 414 rodent and non-rodent species tests are proposed for Hydrocarbons, C10-C13, n-alkanes, isoalkanes, cyclics, aromatics (2-25%). 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 available read across data from a structural analogue, Hydrocarbons, C10-C13, n-alkanes, isoalkanes, cyclics, aromatics (2-25%) does not warrant the 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, further tests (OECD 443 and OECD 414 (rodent and 2nd species)) are proposed on the substance 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
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.